Page last updated: 2024-12-08

pentostatin

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Description

Pentostatin: A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

pentostatin : A member of the class of coformycins that is coformycin in which the hydroxy group at position 2' is replaced with a hydrogen. It is a drug used for the treatment of hairy cell leukaemia. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID439693
CHEMBL ID1580
CHEBI ID27834
SCHEMBL ID2817
MeSH IDM0023987

Synonyms (103)

Synonym
BIDD:GT0136
imidazo(4,5-d)(1,3)diazepin-8-ol, 3-(2-deoxy-d-erythro-pentofuranosyl)-3,4,7,8-tetrahydro-, (8r)-
ci 825
2' deoxycoformycin
HY-A0006
imidazo[4,5-d][1,3]diazepin-8-ol, 3-(2-deoxy-.beta.-d-erythro-pentofuranosyl)-3,4,7,8-tetrahydro-, (8r)-
(r)-3-(2-deoxy-.beta.-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol
2'-deoxycoformycin
2'-dcf
(8r)-3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-7,8-dihydro-6h-imidazo[4,5-d][1,3]diazepin-8-ol
nipent
co-vidarabine
nsc-218321
pd-adi
covidarabine
ci-825
pd-81565
yk-176
cl-67310465
(8r)-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
pentostatin [usan:inn:ban:jan]
pd 81565
imidazo(4,5-d)(1,3)diazepin-8-ol, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,4,7,8-tetrahydro-, (r)-
imidazo(4,5-d)(1,3)diazepin-8-ol, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydro-, (r)-
(r)-deoxycoformycin
pentostatina [inn-spanish]
deaminase, inhibitor for adenosine arabinoside
(r)-2'-deoxycoformycin
hsdb 6547
(r)-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol
pentostatinum [inn-latin]
brn 1223097
8r-2'-deoxycoformycin
pentostatine [inn-french]
(8r)-3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h,6h,7h,8h-imidazo[4,5-d][1,3]diazepin-8-ol
bdbm22925
pentostatin (jan/usan/inn)
D00155
pentostatin
C02267
deoxycoformycin
DB00552
CHEMBL1580
NCGC00182045-01
dtxsid2023436 ,
cas-53910-25-1
dtxcid403436
tox21_113417
A829822
S9521
2'-dexoycoformycin
pentostatinum
unii-395575mzo7
pentostatina
395575mzo7 ,
pentostatine
pentostatin [jan]
pentostatin [mi]
pentostatin [who-dd]
pentostatin [usan]
pentostatin [inn]
pentostatin [hsdb]
pentostatin [orange book]
imidazo(4,5-d)(1,3)diazepin-8-ol, 3-(2-deoxy-.beta.-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydro-, (r)-
pentostatin [mart.]
pentostatin [vandf]
CS-0374
gtpl4805
(8r)-3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h,4h,7h,8h-imidazo[4,5-d][1,3]diazepin-8-ol
(r)-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
FPVKHBSQESCIEP-JQCXWYLXSA-N
SCHEMBL2817
(8r)-3-(2-deoxy-?-d-erythro-pentofuranosyl)-3,4,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
AKOS024456918
pentostatn
J-523899
SR-01000883935-1
sr-01000883935
pentostatin, >=95% (hplc)
pentostatin (ptn)
bdbm223291
mfcd00078802
NCGC00388420-02
pentostatin(deoxycoformycin)
(r)-3-((2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,4,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
AKOS032949742
Q425470
adenosine deaminase inhibitor, dcf - cas 53910-25-1
(r,z)-3-((2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
AMY10324
ci-825;deoxycoformycin
(8r)-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,4,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
(r)-3-((2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
pentostatina (inn-spanish)
pentostatine (inn-french)
(r)-3-(2-deoxy-beta-d-erythro-pento-furanosyl)-3,6,7,8-tetrahydroimidazo
pentostatin (mart.)
2'dcf
pentostatinum (inn-latin)
l01xx08
CHEBI:27834
EN300-222177
Z2204459563

Research Excerpts

Overview

Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase. Pentostatin has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD.

ExcerptReferenceRelevance
"Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. "( [Advances in the biosynthesis of pentostatin].
Duan, X; Liu, H; Lu, X; Song, Z; Tian, Y; Wang, C; Yang, H, 2021
)
2.35
"Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. "( Standard pentostatin dose reductions in renal insufficiency are not adequate: selected patients with steroid-refractory acute graft-versus-host disease.
Dalton, JT; Devine, SM; Edwards, RB; Farag, SS; Grever, MR; Hofmeister, CC; Jansak, BS; Johnston, JS; Lucas, DM; Phelps, MA; Poi, MJ, 2013
)
2.25
"Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses."( Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients.
Abgrall, JF; Benboubker, L; Blaise, AM; Blanc, M; Castaigne, S; Coiffier, B; Divine, M; Gardembas, M; Ghandour, C; Grosbois, B; Harousseau, JL; Lederlin, P; Maloisel, F; Morice, P; Sebban, C, 2003
)
1.35
"Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. "( Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.
Dang, NH; Duvic, M; Fayad, LE; Goy, A; Hagemeister, FB; Huh, YO; Jones, D; McLaughlin, P; Morimoto, C; Pro, B; Rodriguez, MA; Romaguera, JE; Samaniego, F; Samuels, B; Sarris, A; Smith, TL; Tiongson, LP; Tong, AT; Walker, PL; Younes, A,
)
3.02
"Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. "( Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia: a phase I/II study by the Eastern Cooperative Oncology Group study E1488.
Cassileth, PA; Kay, NE; Knospe, W; Lee, S; Oken, MM, 2004
)
3.21
"Pentostatin is a safe and well-tolerated medication, but a dose reduction is required for patients with renal insufficiency."( [Pentostatin treatment for a patient with chronic type adult T-cell leukemia undergoing hemodialysis].
Arima, N; Sugiyama, T, 2005
)
1.96
"Pentostatin is an adenosine deaminase inhibitor used in the treatment of hairy cell leukemia and T-cell lymphomas. "( Possible pentostatin-induced symptomatic hyponatremia.
Bruno, JJ; Canada, TW, 2007
)
2.2
"Pentostatin is an effective agent and induces an excellent response in relapsed HCL patients previously treated with alpha-interferon (alpha-IFN)."( Pentostatin treatment for hairy cell leukemia patients who failed initial therapy with recombinant alpha-interferon: a report of CALGB study 8515.
Budman, D; Dodge, R; Golomb, HM; Horning, SJ; Hutchison, R; Mick, R; Schiffer, CA, 1994
)
2.45
"Pentostatin is a potent inhibitor of adenosine deaminase and is selectively toxic to lymphocytes."( Pentostatin (2'-deoxycoformycin) in the treatment of cutaneous T-cell lymphoma.
Greiner, D; Olsen, EA; Petroni, G, 1997
)
2.46
"Pentostatin is an active agent in heavily pretreated T-cell lymphomas with cutaneous manifestations."( Pentostatin therapy of T-cell lymphomas with cutaneous manifestations.
Duvic, M; Kurzrock, R; Pilat, S, 1999
)
3.19
"Pentostatin is a highly effective agent for hairy cell leukemia and produces prolonged remissions in the majority of patients."( Long-term outcome following treatment of hairy cell leukemia with pentostatin (Nipent): a National Cancer Institute of Canada study.
Corbett, WE; Daeninck, PJ; Eisenhauer, E; Johnston, JB; Wainman, N; Zaentz, SD, 2000
)
1.27
"Pentostatin is an active agent in this group of diseases and merits further exploration."( Pentostatin (Nipent) in T-cell lymphomas.
Kurzrock, R, 2000
)
2.47
"Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses."( Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin.
Appelbaum, F; Bennett, JM; Cassileth, P; Cheson, B; Corbett, W; Eisenhauer, E; Flinn, IW; Foucar, MK; Golomb, H; Grever, MR; Habermann, T; Head, D; Hutchison, R; Kopecky, KJ; Rai, K, 2000
)
1.24
"Pentostatin is a highly lymphocytotoxic agent active in hairy cell leukemia. "( Therapy of T cell lymphomas with pentostatin.
Kurzrock, R, 2001
)
2.03
"Pentostatin is a purine analog that inhibits adenosine deaminase, a key enzyme necessary for purine salvage. "( Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.
Kane, BJ; Kuhn, JG; Roush, MK,
)
3.02
"Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action."( The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies.
Spiers, AS, 1987
)
1.37

Effects

Pentostatin (Nipent) has demonstrated significant activity as a single agent in patients with low-grade B- and T-cell lymphomas. Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa.

ExcerptReferenceRelevance
"That pentostatin, which has been reported to inhibit adenosine deaminase, combining cordycepin could enhance the efficiency of cordycepin in vivo."( Cordycepin and pentostatin biosynthesis gene identified through transcriptome and proteomics analysis of Cordyceps kyushuensis Kob.
Li, C; Ling, J; Zhang, G; Zhao, X, 2019
)
1.32
"Pentostatin has also been shown to have clinical activity in CLL and appears to be less toxic than its fludarabine counterpart, which may offer some important advantages."( Pentostatin treatment combinations in chronic lymphocytic leukemia.
Kay, NE; Lamanna, N, 2009
)
2.52
"Pentostatin has activity in refractory chronic GVHD in children, and future studies, including treatment of children newly diagnosed with high-risk chronic GVHD, are warranted."( Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study.
Browning, B; Gilman, AL; Grimley, M; Jacobsohn, DA; Lehmann, L; Nemecek, ER; Rademaker, A; Schultz, KR; Thormann, K; Vogelsang, GB, 2009
)
1.43
"Pentostatin has been used to treat cGVHD in a small series of pediatric patients."( Pentostatin for the treatment of chronic graft-versus-host disease in children.
Anders, V; Chen, AR; Goldberg, JD; Jacobsohn, DA; Margolis, J; Phelps, M; Vogelsang, GB, 2003
)
2.48
"Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell lymphoma-leukemia, and low grade non-Hodgkin's lymphomas."( Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases.
Spiers, AS, 1996
)
1.35
"Pentostatin has activity in patients with steroid-refractory aGVHD that is worth exploring in future trials."( Pentostatin in steroid-refractory acute graft-versus-host disease.
Anders, V; Bolaños-Meade, J; Byrd, JC; Grever, MR; Jacobsohn, DA; Lucas, DM; Margolis, J; Ogden, A; Phelps, M; Vogelsang, GB; Wientjes, MG, 2005
)
2.49
"Pentostatin has demonstrated significant activity as a single agent in patients with low-grade B-cell and T-cell lymphomas and is less myelosuppressive than other purine analogues."( Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma.
Hensel, M; Ho, AD; Kornacker, M; Krasniqi, F; Villalobos, M, 2005
)
3.21
"Pentostatin has been shown to be active in a variety of B- and T-cell malignancies. "( Pentostatin and purine analogs for indolent lymphoid malignancies.
Hensel, M; Ho, AD, 2006
)
3.22
"Pentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD."( Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease.
Anders, V; Bolaños-Meade, J; Chen, AR; Higman, M; Jacobsohn, DA; Kaup, M; Margolis, J; Piantadosi, S; Vogelsang, GB; Zahurak, M, 2007
)
2.12
"Pentostatin (Nipent) has demonstrated significant activity as a single agent in patients with low-grade B- and T-cell lymphomas, but thus far, clinical experience with combinations of pentostatin and other agents is limited. "( Combination therapy with purine nucleoside analogs.
Foss, FM, 2000
)
1.75
"Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa."( Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.
Kane, BJ; Kuhn, JG; Roush, MK,
)
2.3

Actions

ExcerptReferenceRelevance
"Pentostatin was used to inhibit adenosine deaminase, and coformycin was used to inhibit AMP deaminase in experiments designed to delineate the metabolic fate of 3a."( Synthesis and biochemical properties of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine.
Allan, PW; Bennett, LL; Chang, CH; Montgomery, JA; Rose, LM; Secrist, JA, 1986
)
0.99

Treatment

ExcerptReferenceRelevance
"Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62 +/- 30.2 microM vs."( Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size.
Gallagher, KP; Martin, BJ; McClanahan, TB; Van Wylen, DG, 1997
)
0.62

Toxicity

Pentostatin (Nipent; SuperGen, San Ramon, CA) is a safe and well-tolerated medication. Like all chemotherapeutic agents, it may be associated with some toxicity.

ExcerptReferenceRelevance
" Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses."( Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits.
Anderson, JA; Bleck, J; Brown, S; Dostal, LA, 1991
)
0.82
" The combination dCF + cordycepin and alkylating agent mafosfamide were, however, toxic to all the cell lines at the concentrations employed, as well as to CFU-GM and CFU-GEMM."( Selective toxicity of purine nucleosides to human leukaemic cells.
Ganeshaguru, K; Green, ES; Hoffbrand, AV; Piga, A; Sheridan, B, 1989
)
0.28
"Deoxyadenosine is known to be toxic to both proliferating and resting lymphocytes that lack adenosine deaminase (ADA) activity."( Profound toxicity of deoxyadenosine and 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo.
Carrera, CJ; Carson, DA; Lotz, M; Piro, LD; Yamanaka, H, 1989
)
0.28
"Deoxyadenosine has been implicated as the toxic metabolite causing profound lymphopenia in immunodeficient children with a genetic deficiency of adenosine deaminase (ADA), and in adults treated with the potent ADA inhibitor deoxycoformycin."( Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes.
Carrera, CJ; Carson, DA; Kubota, M; Seto, S; Wasson, DB, 1985
)
0.27
" If dATP is the toxic metabolic accumulated in the malignant cells of patients treated with dCf, we propose that AdR supplementation of treatment should be considered with extreme caution since severe damage to normal tissues might result."( Toxicity and immunosuppressive activity of binary combinations of 2'-deoxycoformycin and 2'-deoxyadenosine.
Clink, HM; Harrap, KR; Kohn, J; McGhee, KG; Neville, AM; Paine, RM; Weston, BJ,
)
0.13
" Deoxyadenosine was the most toxic in all the systems, the LD50 values being 20-25 microM."( Adenosine and deoxyadenosine toxicity in colony assay systems for human T-lymphocytes, B-lymphocytes, and granulocytes.
Belch, A; Brox, LW; Pollock, E, 1982
)
0.26
" In addition, case records from National Cancer Institute (NCI) Group C protocols were reviewed for fludarabine in chronic lymphocytic leukemia (CLL), and cladribine and pentostatin in hairy cell leukemia (HCL), as well as adverse drug reactions reported to the NCI from January 1980 through September 1993."( Neurotoxicity of purine analogs: a review.
Cheson, BD; Foss, FM; Sorensen, JM; Vena, DA, 1994
)
0.48
" In the FAMP group, a direct correlation was found between the LD50 values of both FAMP and Mitox and the number of synergistic interactions, while the Pearson correlation coefficient was not significant in the Pento group."( The in vitro cytotoxic effect of mitoxantrone in combination with fludarabine or pentostatin in B-cell chronic lymphocytic leukemia.
Brugiatelli, M; Callea, I; Console, G; Filangeri, M; Iacopino, P; Morabito, F; Musolino, C; Oliva, B; Sculli, G; Stelitano, C,
)
0.36
" In this paper we demonstrate that the observed toxic effect is strictly dependent on cell density."( Deoxyadenosine metabolism in a human colon-carcinoma cell line (LoVo) in relation to its cytotoxic effect in combination with deoxycoformycin.
Banditelli, S; Bemi, V; Camici, M; Giorgelli, F; Mattana, A; Pesi, R; Sgarrella, F; Tazzni, N; Tozzi, MG; Turchi, G, 1998
)
0.3
"Pentostatin (Nipent; SuperGen, San Ramon, CA) is a safe and well-tolerated medication but, like all chemotherapeutic agents, it may be associated with some toxicity."( Pentostatin (Nipent): a review of potential toxicity and its management.
Grever, MR; Margolis, J, 2000
)
3.19
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32
" We have provided evidence that PER is a safe and effective regimen for WM."( Pentostatin, cyclophosphamide and rituximab is a safe and effective treatment in patients with Waldenström's macroglobulinemia.
Dreyling, M; Hensel, M; Herth, I; Hiddemann, W; Ho, AD; Horstmann, K; Koniczek, S; Rieger, M; Witzens-Harig, M, 2015
)
1.86

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic parameters are determined by a sequential optimization scheme in which each tissue is studied by means of a hybrid model."( Physiologic model for the pharmacokinetics of 2'deoxycoformycin in normal and leukemic mice.
Dedrick, RL; King, FG, 1981
)
0.26
"The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients in order to establish dosing guidelines for this population."( Pentostatin pharmacokinetics and dosing recommendations in patients with mild renal impairment.
Fleming, GF; Lathia, C; Meyer, M; Ratain, MJ; Whitfield, L, 2002
)
1.99
"Enrolled in the study were 13 patients (7 IRF and 6 NRF), of whom 12 contributed samples for pharmacokinetic analysis."( Pentostatin pharmacokinetics and dosing recommendations in patients with mild renal impairment.
Fleming, GF; Lathia, C; Meyer, M; Ratain, MJ; Whitfield, L, 2002
)
1.76

Compound-Compound Interactions

Pentostatin (I) was evaluated in combination with the partially effective antitumor nucleoside N6-(delta 2-isopentenyl)adenosine (II) for cytotoxic activity against cultured L-1210 lymphocytic mouse leukemia cells.

ExcerptReferenceRelevance
"Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A)."( Lack of significant activity of 2'-deoxycoformycin alone or in combination with adenine arabinoside in relapsed childhood acute lymphoblastic leukemia. A randomized phase II trial from the Childrens Cancer Study Group.
Blatt, J; Hammond, GD; Krailo, MD; Miser, JS; Reaman, GH; Roloff, J, 1992
)
0.28
"The toxicology and pharmacology of formycin both as a single agent and combined with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF) were examined in outbred Swiss mice heterozygous for the nude gene (nu/+)."( Biochemical pharmacology and toxicology of formycin alone and in combination with 2'-deoxycoformycin (pentostatin).
Calabresi, P; Chu, SH; Crabtree, GW; Dexter, DL; Diamond, I; Farineau, DM; Ghoda, LY; McGowan, DL; Parks, RE; Spremulli, EN, 1983
)
0.48
"Pentostatin (I), a tight-binding inhibitor of adenosine deaminase, was evaluated in combination with the partially effective antitumor nucleoside N6-(delta 2-isopentenyl)adenosine (II) for cytotoxic activity against cultured L-1210 lymphocytic mouse leukemia cells."( Increased cytotoxicity of N6-(delta 2-isopentenyl)adenosine in combination with pentostatin against L-1210 leukemia cells.
Chang, Y; Hacker, B, 1983
)
1.94
"The biologic effects of a series of sugar-substituted analogs of tubercidin were evaluated and compared with the effects of the homologous series of adenosine analogs in combination with 2'-deoxycoformycin."( Comparison of the effects on cultured L1210 leukemia cells of the ribosyl, 2'-deoxyribosyl, and xylosyl homologs of tubercidin and adenosine alone or in combination with 2'-deoxycoformycin.
Cass, CE; Muhs, WH; Robins, MJ; Selner, M; Tan, TH, 1982
)
0.26
"The toxicology and metabolism of 8-azaadenosine (8-azaAdo) were examined both as a single agent and in combination with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF)."( Biochemical pharmacology and toxicology of 8-azaadenosine alone and in combination with 2'-deoxycoformycin (pentostatin).
Calabresi, P; Chu, SH; Crabtree, GW; Dexter, DL; Diamond, I; Farineau, DM; Ghoda, LY; McGowan, DL; Parks, RE; Spremulli, EN, 1982
)
0.48
" The drug induced functional and morphologic differentiation of myeloid leukemia cells in combination with 2'-deoxyadenosine (dAd), but not dCF alone."( Induction of differentiation of human myeloid leukemia cells by 2'-deoxycoformycin in combination with 2'-deoxyadenosine.
Honma, Y; Niitsu, N; Umeda, M, 1997
)
0.3
" Cordycepin in combination with dCF produced symptoms associated with severe gastrointestinal toxicity (decreased body weights, emesis, diarrhea, decreased food consumption, and necrosis of the gastrointestinal tract) and bone marrow toxicity (lymphopenia, thrombocytopenia, and depletion of hematopoietic cells)."( Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs.
Allan, PW; Coyne, JM; Duncan, KL; Farnell, DR; Hill, DL; Page, JG; Rodman, LE; Smith, AC; Tomaszewski, JE, 1997
)
0.3
" It is possible that lamivudine combined with chemotherapy may have had a therapeutic effect on ATL in this case."( [Development of acute type, CD 8 positive adult T-cell leukemia in a carrier of hepatitis B virus--possible therapeutic effect of lamivudine combined with chemotherapy].
Hasegawa, H; Miyagi, T; Nagasaki, A; Nakachi, S; Shinzato, O; Taira, N; Takasu, N; Tomoyose, T, 2006
)
0.33
" In the current study, nine dogs received conditioning with 920 cGy TBI and postgrafting MTX either with ECP on days -2 to -1 alone (n=5) or ECP on days -6 and -5 combined with two doses of pentostatin (days -4 to -3) (n=4)."( Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD.
Bethge, WA; Gooley, T; Kerbauy, FR; Sandmaier, BM; Santos, EB; Storb, R, 2014
)
0.86

Bioavailability

ExcerptReferenceRelevance
"5-fold lower than Plumen, (84 +/- 12) x 10(-6) cm/s, which means that 77 +/- 6% of 6-Cl-ddP was metabolized during its intestinal transport, thus qualitatively accounting for the low oral bioavailability (7%) of 6-Cl-ddP observed in vivo in rats."( Absorption and intestinal metabolism of purine dideoxynucleosides and an adenosine deaminase-activated prodrug of 2',3'-dideoxyinosine in the mesenteric vein cannulated rat ileum.
Anderson, BD; Ho, NF; Singhal, D, 1998
)
0.3
"From metabolic considerations and prediction of an inhibitor-induced conformational change, novel adenosine deaminase (ADA) inhibitors with improved activities and oral bioavailability have been developed on the basis of our originally designed non-nucleoside ADA inhibitors."( Rational design of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors: predicting enzyme conformational change and metabolism.
Inoue, T; Kato, T; Kato, Y; Kinoshita, T; Kuno, M; Nakamura, K; Nakanishi, I; Tanaka, K; Terasaka, T; Tsuji, K, 2005
)
0.33
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days for another 6 weeks.

ExcerptRelevanceReference
"To review the pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin, and to evaluate the role of pentostatin in the treatment of hairy cell leukemia (HCL)."( Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.
Kane, BJ; Kuhn, JG; Roush, MK,
)
1.79
" When dosed appropriately, pentostatin is generally well tolerated."( Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.
Kane, BJ; Kuhn, JG; Roush, MK,
)
1.87
" Pentostatin appears to be quite stable after reconstitution of a lyophilized experimental dosage form."( Chemical stability of pentostatin (NSC-218321), a cytotoxic and immunosuppressant agent.
al-Razzak, LA; Benedetti, AE; Stella, VJ; Waugh, WN, 1990
)
1.5
" Pentostatin was administered at a dosage of 4 mg/m2 weekly for 3 weeks, then 4 mg/m2 every other week for 6 weeks and once a month for 6 months."( Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer.
Coiffier, B; deCataldo, F; Ho, AD; Lechner, K; Luciani, M; Peetermans, ME; Rodenhuis, S; Sonneveld, P; Stryckmans, P; Thaler, J, 1990
)
2.63
" Further investigations of antitumor efficacy with the use of this low dosage schedule should continue in patients with hematologic neoplasms, and additional preliminary studies of the combination of an adenosine deaminase inhibitor with an adenosine analog should also be considered."( Clinical, pharmacologic, and immunologic effects of 2'-deoxycoformycin.
Calabresi, P; Crabtree, GW; Cummings, FJ; Parks, RE; Spremulli, EN; Wiemann, MC, 1988
)
0.27
" Cells were treated in a dose-response manner for 72 hr and the concentration of drug necessary to inhibit cell growth 50% (GI50) was determined."( Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells.
Hubbell, HR; Lee, C; Pequignot, EC; Suhadolnik, RJ; Willis, DH, 1985
)
0.27
" None of the dosing regimens had any effect on anticollagen antibody titer."( Effects of pentostatin (2'deoxycoformycin), an inhibitor of adenosine deaminase, on type II collagen-induced arthritis in rats.
Gilbertsen, RB, 1985
)
0.66
" A dose-response analysis demonstrated that the concentration of deoxycoformycin at which there was 50% inhibition of growth was greater than 1 X 10(-3) M in lymphoblastoid cells."( In vitro metabolism of deoxycoformycin in human T lymphoblastoid cells. Phosphorylation of deoxycoformycin and incorporation into cellular DNA.
Coleman, MS; Siaw, MF, 1984
)
0.27
" Dosage appeared to have no effect on the rate of recovery of the deoxycoformycin-inhibited enzyme but marked tissue differences were observed."( Deoxycoformycin toxicity in mice after long-term treatment.
Agarwal, RP, 1980
)
0.26
" Drug dosage was modified in 39 (51%) of 76 evaluable patients."( Pentostatin treatment for hairy cell leukemia patients who failed initial therapy with recombinant alpha-interferon: a report of CALGB study 8515.
Budman, D; Dodge, R; Golomb, HM; Horning, SJ; Hutchison, R; Mick, R; Schiffer, CA, 1994
)
1.73
"Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses."( Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group.
Bödewadt-Radzun, S; de Witte, T; Döhner, H; Ho, AD; Lauria, F; Lechner, K; Sonneveld, P; Stryckmans, P; Suciu, S; Thaler, J, 1993
)
1.73
" weekly for 3 weeks and then every 14 days to be followed after 3 doses by the same dosage every 4 weeks until maximum response or progression."( Pentostatin (2'-deoxycoformycin, dCF) in patients with low-grade (B-T-cell) and intermediate- and high-grade (T-cell) malignant lymphomas: phase II study of the EORTC Early Clinical Trials Group.
Cavalli, F; Cerny, TH; Kaye, S; Monfardini, S; Smyth, JF; Sorio, R; Van Glabbeke, M,
)
1.57
" To test the hypothesis that plasma adenosine deaminase, which was increased in the patients' plasma, was actually involved in this blunted response to adenosine in alcoholic cirrhosis, we performed adenosine dose-response experiments and pharmacologically blocked adenosine deaminase activity with deoxycoformycin."( Blunted anti-inflammatory response to adenosine in alcoholic cirrhosis.
Devière, J; Gulbis, B; Le Moine, O; Quertinmont, E, 1999
)
0.3
" Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then 4 mg/m2 every 14 days for another 6 weeks, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months."( Pentostatin in T-cell malignancies--a phase II trial of the EORTC. Leukemia Cooperative Group.
Dardenne, M; De Cataldo, F; Döhner, H; Ho, AD; Peetermans, M; Solbu, G; Stryckmans, P; Suciu, S; Thaler, J; Willemze, R; Zittoun, R, 1999
)
2.66
" Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months."( Pentostatin (Nipent) in T-cell malignancies. Leukemia Cooperative Group and the European Organization for Research and Treatment of Cancer.
Dardenne, M; De Cataldo, F; Döhner, H; Ho, AD; Peetermans, M; Solbu, G; Stryckmans, P; Suciu, S; Thaler, J; Willemze, R; Zittoun, R, 2000
)
2.66
"The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients in order to establish dosing guidelines for this population."( Pentostatin pharmacokinetics and dosing recommendations in patients with mild renal impairment.
Fleming, GF; Lathia, C; Meyer, M; Ratain, MJ; Whitfield, L, 2002
)
1.99
" The most commonly studied regimens have utilized fludarabine, but severe myelosuppression and immunosuppression of these combinations require close attention to dosing and schedule."( Purine analogue-based chemotherapy regimens for second-line therapy in patients with chronic lymphocytic leukemia.
Lamanna, N; Weiss, MA, 2006
)
0.33
" Because of its simplified dosing schedule, cladribine is commonly used as the initial therapy."( Hairy cell leukemia: an elusive but treatable disease.
de Castro, C; Wanko, SO,
)
0.13
" Newer methods of cladribine administration and modified dosing schedules have since been studied."( My treatment approach to hairy cell leukemia.
Naik, RR; Saven, A, 2012
)
0.38
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
EC 3.5.4.4 (adenosine deaminase) inhibitorAn EC 3.5.4.* (non-peptide cyclic amidine C-N hydrolase) inhibitor that interferes with the action of adenosine deaminase (EC 3.5.4.4).
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
antimetaboliteA substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
bacterial metaboliteAny prokaryotic metabolite produced during a metabolic reaction in bacteria.
Aspergillus metaboliteAny fungal metabolite produced during a metabolic reaction in the mould, Aspergillus.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
coformycins
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Bile salt export pumpHomo sapiens (human)IC50 (µMol)133.00000.11007.190310.0000AID1473738
Adenosine deaminaseHomo sapiens (human)Ki0.00010.00000.30887.0000AID1578774; AID1578775; AID1798270; AID1895862; AID33846; AID33849; AID33969; AID717435
Adenosine deaminase Bos taurus (cattle)Ki0.00000.00000.48937.0000AID33656; AID33670
Adenosine deaminase Plasmodium falciparum (malaria parasite P. falciparum)Ki0.00410.00000.00180.0082AID1578776; AID1578777
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (79)

Processvia Protein(s)Taxonomy
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
adenosine catabolic processAdenosine deaminaseHomo sapiens (human)
inosine biosynthetic processAdenosine deaminaseHomo sapiens (human)
allantoin metabolic processAdenosine deaminaseHomo sapiens (human)
response to hypoxiaAdenosine deaminaseHomo sapiens (human)
trophectodermal cell differentiationAdenosine deaminaseHomo sapiens (human)
liver developmentAdenosine deaminaseHomo sapiens (human)
placenta developmentAdenosine deaminaseHomo sapiens (human)
germinal center B cell differentiationAdenosine deaminaseHomo sapiens (human)
germinal center formationAdenosine deaminaseHomo sapiens (human)
positive regulation of germinal center formationAdenosine deaminaseHomo sapiens (human)
negative regulation of leukocyte migrationAdenosine deaminaseHomo sapiens (human)
mature B cell apoptotic processAdenosine deaminaseHomo sapiens (human)
negative regulation of mature B cell apoptotic processAdenosine deaminaseHomo sapiens (human)
adenosine catabolic processAdenosine deaminaseHomo sapiens (human)
deoxyadenosine catabolic processAdenosine deaminaseHomo sapiens (human)
AMP catabolic processAdenosine deaminaseHomo sapiens (human)
xenobiotic metabolic processAdenosine deaminaseHomo sapiens (human)
smooth muscle contractionAdenosine deaminaseHomo sapiens (human)
cell adhesionAdenosine deaminaseHomo sapiens (human)
response to inorganic substanceAdenosine deaminaseHomo sapiens (human)
positive regulation of heart rateAdenosine deaminaseHomo sapiens (human)
response to purine-containing compoundAdenosine deaminaseHomo sapiens (human)
calcium-mediated signalingAdenosine deaminaseHomo sapiens (human)
positive regulation of B cell proliferationAdenosine deaminaseHomo sapiens (human)
purine nucleotide salvageAdenosine deaminaseHomo sapiens (human)
GMP salvageAdenosine deaminaseHomo sapiens (human)
T cell differentiation in thymusAdenosine deaminaseHomo sapiens (human)
positive regulation of T cell differentiation in thymusAdenosine deaminaseHomo sapiens (human)
regulation of cell-cell adhesion mediated by integrinAdenosine deaminaseHomo sapiens (human)
B cell proliferationAdenosine deaminaseHomo sapiens (human)
T cell activationAdenosine deaminaseHomo sapiens (human)
penile erectionAdenosine deaminaseHomo sapiens (human)
purine-containing compound salvageAdenosine deaminaseHomo sapiens (human)
amide catabolic processAdenosine deaminaseHomo sapiens (human)
AMP salvageAdenosine deaminaseHomo sapiens (human)
positive regulation of smooth muscle contractionAdenosine deaminaseHomo sapiens (human)
dAMP catabolic processAdenosine deaminaseHomo sapiens (human)
dATP catabolic processAdenosine deaminaseHomo sapiens (human)
adenosine metabolic processAdenosine deaminaseHomo sapiens (human)
inosine biosynthetic processAdenosine deaminaseHomo sapiens (human)
xanthine biosynthetic processAdenosine deaminaseHomo sapiens (human)
alpha-beta T cell differentiationAdenosine deaminaseHomo sapiens (human)
positive regulation of alpha-beta T cell differentiationAdenosine deaminaseHomo sapiens (human)
lung alveolus developmentAdenosine deaminaseHomo sapiens (human)
Peyer's patch developmentAdenosine deaminaseHomo sapiens (human)
embryonic digestive tract developmentAdenosine deaminaseHomo sapiens (human)
negative regulation of inflammatory responseAdenosine deaminaseHomo sapiens (human)
positive regulation of calcium-mediated signalingAdenosine deaminaseHomo sapiens (human)
T cell receptor signaling pathwayAdenosine deaminaseHomo sapiens (human)
positive regulation of T cell receptor signaling pathwayAdenosine deaminaseHomo sapiens (human)
leukocyte migrationAdenosine deaminaseHomo sapiens (human)
negative regulation of adenosine receptor signaling pathwayAdenosine deaminaseHomo sapiens (human)
negative regulation of penile erectionAdenosine deaminaseHomo sapiens (human)
thymocyte apoptotic processAdenosine deaminaseHomo sapiens (human)
negative regulation of thymocyte apoptotic processAdenosine deaminaseHomo sapiens (human)
mucus secretionAdenosine deaminaseHomo sapiens (human)
negative regulation of mucus secretionAdenosine deaminaseHomo sapiens (human)
hypoxanthine salvageAdenosine deaminaseHomo sapiens (human)
adenosine catabolic processAdenosine deaminase Bos taurus (cattle)
cell adhesionAdenosine deaminase Bos taurus (cattle)
nucleotide metabolic processAdenosine deaminase Bos taurus (cattle)
purine ribonucleoside monophosphate biosynthetic processAdenosine deaminase Bos taurus (cattle)
inosine biosynthetic processAdenosine deaminase Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (12)

Processvia Protein(s)Taxonomy
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
adenosine deaminase activityAdenosine deaminaseHomo sapiens (human)
protein bindingAdenosine deaminaseHomo sapiens (human)
zinc ion bindingAdenosine deaminaseHomo sapiens (human)
deaminase activityAdenosine deaminaseHomo sapiens (human)
2'-deoxyadenosine deaminase activityAdenosine deaminaseHomo sapiens (human)
adenosine deaminase activityAdenosine deaminase Bos taurus (cattle)
protein bindingAdenosine deaminase Bos taurus (cattle)
zinc ion bindingAdenosine deaminase Bos taurus (cattle)
2'-deoxyadenosine deaminase activityAdenosine deaminase Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
lysosomeAdenosine deaminaseHomo sapiens (human)
cytosolAdenosine deaminaseHomo sapiens (human)
plasma membraneAdenosine deaminaseHomo sapiens (human)
external side of plasma membraneAdenosine deaminaseHomo sapiens (human)
cell surfaceAdenosine deaminaseHomo sapiens (human)
membraneAdenosine deaminaseHomo sapiens (human)
cytoplasmic vesicle lumenAdenosine deaminaseHomo sapiens (human)
anchoring junctionAdenosine deaminaseHomo sapiens (human)
cytosolAdenosine deaminaseHomo sapiens (human)
external side of plasma membraneAdenosine deaminaseHomo sapiens (human)
lysosomeAdenosine deaminase Bos taurus (cattle)
cytoplasmic vesicle lumenAdenosine deaminase Bos taurus (cattle)
anchoring junctionAdenosine deaminase Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (87)

Assay IDTitleYearJournalArticle
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1578777Inhibition of Plasmodium falciparum N-terminal thrombin cleavable His6-tagged ADA expressed in Escherichia coli BL21 assessed as equilibrium dissociation constant by measuring reduction in formation of inosine using adenosine as substrate2019Journal of medicinal chemistry, 09-26, Volume: 62, Issue:18
Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473740Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID8593Pharmacokinetic property (AUC) was determined after ip administration of 32 mg/kg in mice2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1174822Cytotoxicity against human T47D cells at 2.5 to 40 uM after 72 hrs by SRB assay2015European journal of medicinal chemistry, Jan-07, Volume: 89Synthesis of novel substituted purine derivatives and identification of the cell death mechanism.
AID33829Relative enzyme affinity for adenosine deaminase was determined; No data1982Journal of medicinal chemistry, May, Volume: 25, Issue:5
Inhibitors of adenosine deaminase. Studies in combining high-affinity enzyme-binding structural units. erythro-1,6-Dihydro-6-(hydroxymethyl)-9-(2-hydroxy-3-nonyl)purine and erythro-9-(2-hydroxy-3-nonyl)purine.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID33670Compound was tested for the inhibition of adenosine deaminase from calf intestine; Range of 0.01-0.001 nM1994Journal of medicinal chemistry, Jan-07, Volume: 37, Issue:1
Adenosine deaminase inhibitors: synthesis and structure-activity relationships of 2-hydroxy-3-nonyl derivatives of azoles.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID717435Inhibition of adenosine deaminase2012Bioorganic & medicinal chemistry letters, Dec-01, Volume: 22, Issue:23
Investigations into specificity of azepinomycin for inhibition of guanase: discrimination between the natural heterocyclic inhibitor and its synthetic nucleoside analogues.
AID1578774Inhibition of human erythrocytes ADA assessed as reduction in formation of inosine using adenosine as substrate2019Journal of medicinal chemistry, 09-26, Volume: 62, Issue:18
Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.
AID33969The compound was tested in vitro for inhibition of human erythrocytic adenosine deaminase.1983Journal of medicinal chemistry, Oct, Volume: 26, Issue:10
Adenosine deaminase inhibitors. Synthesis and biological evaluation of (+/-)-3,6,7,8-tetrahydro-3-[(2-hydroxyethoxy)methyl]imidazo[4,5-d] [1,3]diazepin-8-ol and some selected C-5 homologues of pentostatin.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1174821Cytotoxicity against human HCT116 cells at 2.5 to 40 uM after 72 hrs by SRB assay2015European journal of medicinal chemistry, Jan-07, Volume: 89Synthesis of novel substituted purine derivatives and identification of the cell death mechanism.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID409957Inhibition of bovine liver MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID33658Binding affinity against calf intestine adenosine deaminase enzyme; 10E-11 to 10e-12 M1984Journal of medicinal chemistry, Mar, Volume: 27, Issue:3
Adenosine deaminase inhibitors. Synthesis of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine.
AID1473741Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1895862Binding affinity to human erythrocytic ADA assessed as inhibition constant by spectrophotometric analysis2021European journal of medicinal chemistry, Dec-15, Volume: 226Zinc enzymes in medicinal chemistry.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1174820Cytotoxicity against human HuH7 cells at 2.5 to 40 uM after 72 hrs by SRB assay2015European journal of medicinal chemistry, Jan-07, Volume: 89Synthesis of novel substituted purine derivatives and identification of the cell death mechanism.
AID1578776Inhibition of Plasmodium falciparum N-terminal thrombin cleavable His6-tagged ADA expressed in Escherichia coli BL21 assessed as reduction in formation of inosine using adenosine as substrate2019Journal of medicinal chemistry, 09-26, Volume: 62, Issue:18
Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.
AID33846Compound was evaluated for the inhibition of adenosine deaminase1981Journal of medicinal chemistry, Dec, Volume: 24, Issue:12
Adenosine deaminase inhibitors. Conversion of a single chiral synthon into erythro- and threo-9-(2-hydroxy-3-nonyl)adenines.
AID477295Octanol-water partition coefficient, log P of the compound2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
QSPR modeling of octanol/water partition coefficient of antineoplastic agents by balance of correlations.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID33661Binding affinity towards calf spleen adenosine deaminase was determined2004Journal of medicinal chemistry, Feb-12, Volume: 47, Issue:4
Inhibition of adenosine deaminase by novel 5:7 fused heterocycles containing the imidazo[4,5-e][1,2,4]triazepine ring system: a structure-activity relationship study.
AID1473739Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID33660Binding affinity against Adenosine deaminase from calf intestinal mucosa was determined2001Bioorganic & medicinal chemistry letters, Nov-19, Volume: 11, Issue:22
A unique ring-expanded acyclic nucleoside analogue that inhibits both adenosine deaminase (ADA) and guanine deaminase (GDA; guanase): synthesis and enzyme inhibition studies of 4,6-diamino-8H-1-hydroxyethoxymethyl-8-iminoimidazo[4,5-e][1,3]diazepine.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID116409Antitumor activity after administration (p.o.) in mice U937 cells at a dose of 0.25 mg/kg2004Journal of medicinal chemistry, May-20, Volume: 47, Issue:11
Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.
AID245705Antitumor activity (0.25 mg/kg, i.p.) on lymphoma U-937 tumor growth inoculated in mice2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Rational design of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors: predicting enzyme conformational change and metabolism.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID9760Pharmacokinetic property (C(max)) was determined after ip administration of 32 mg/kg in mice2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
AID1473738Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID33849Inhibition constant against human adenosine deaminase was determined2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
AID98360Compound was evaluated for the cytotoxicity against L1210 cells in absence of coformycin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Synthesis and biochemical properties of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID33656Binding affinity (Ki) at calf intestinal adenosine deaminase.1992Journal of medicinal chemistry, Oct-30, Volume: 35, Issue:22
Adenosine deaminase inhibitors. Synthesis and biological evaluation of C1' and nor-C1' derivatives of (+)-erythro-9-(2(S)-hydroxy-3(R)-nonyl)adenine.
AID245704Antitumor activity (2.5, i.p.) on lymphoma U-937 tumor growth inoculated in mice2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Rational design of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors: predicting enzyme conformational change and metabolism.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID98361Compound was evaluated for the cytotoxicity against L1210 cells in presence of coformycin1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Synthesis and biochemical properties of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID116411Antitumor activity after administration (p.o.) in mice U937 cells at a dose of 2.5 mg/kg2004Journal of medicinal chemistry, May-20, Volume: 47, Issue:11
Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.
AID116408Antitumor activity after administration (i.p.) in mice U937 cells at a dose of 0.025 mg/kg2004Journal of medicinal chemistry, May-20, Volume: 47, Issue:11
Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1578775Inhibition of human erythrocytes ADA assessed as equilibrium dissociation constant by measuring reduction in formation of inosine using adenosine as substrate2019Journal of medicinal chemistry, 09-26, Volume: 62, Issue:18
Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1802653In Vitro ADA Activity Assay from Article 10.1016/j.chembiol.2016.12.012: \\An Unusual Protector-Protu00E9gu00E9 Strategy for the Biosynthesis of Purine Nucleoside Antibiotics.\\2017Cell chemical biology, Feb-16, Volume: 24, Issue:2
An Unusual Protector-Protégé Strategy for the Biosynthesis of Purine Nucleoside Antibiotics.
AID1345150Human Adenosine deaminase (Adenosine turnover)1977Biochemical pharmacology, Mar-01, Volume: 26, Issue:5
Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors.
AID1798270ADA Inhibition Assay from Article 10.1016/S0960-894X(03)00026-X: \\Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.\\2003Bioorganic & medicinal chemistry letters, Mar-24, Volume: 13, Issue:6
Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (972)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990355 (36.52)18.7374
1990's291 (29.94)18.2507
2000's193 (19.86)29.6817
2010's114 (11.73)24.3611
2020's19 (1.95)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 45.07

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index45.07 (24.57)
Research Supply Index7.01 (2.92)
Research Growth Index4.34 (4.65)
Search Engine Demand Index72.50 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (45.07)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials102 (10.11%)5.53%
Reviews170 (16.85%)6.00%
Case Studies121 (11.99%)4.05%
Observational2 (0.20%)0.25%
Other614 (60.85%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (45)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Initial Systemic Treatment of Acute GVHD: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox (ONTAK), and Pentostatin in Combination With Corticosteroids (BMT CTN #0302) [NCT00224874]Phase 2180 participants (Actual)Interventional2005-09-30Completed
Allogeneic Peripheral Blood Stem Cell Transplantation With Minimally Myelosuppressive Regimen of Pentostatin and Low-dose Total-body Irradiation [NCT00571662]Phase 276 participants (Actual)Interventional2000-12-08Completed
"A Single-Center, Open-Label Study to Evaluate the Safety and Efficacy of Nipent, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated and Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin's Lymphoma or Bulky Lymphoma" [NCT00496873]Phase 2100 participants (Actual)Interventional2005-06-30Completed
Phase I Trial With Cohort Expansion of Pentostatin, Bendamustine and Ofatumumab (PBO) for the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma [NCT01352312]Phase 110 participants (Actual)Interventional2011-05-25Terminated(stopped due to Insufficient accrual over 12 mo period)
A Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Severe Aplastic Anemia Patients With COH-MC-17: A Non-Myeloablative/ Reduced-Intensity, Conditioning Regimen and CD4+ T-Cell-Depleted Haploidentical Hematopoietic Tran [NCT05757310]Phase 16 participants (Anticipated)Interventional2024-04-01Recruiting
Phase II Study of Pentostatin With Cyclophosphamide and Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia [NCT00541034]Phase 249 participants (Actual)Interventional2005-05-31Completed
A Single-arm Multi-center Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia [NCT01681563]Phase 247 participants (Actual)Interventional2011-09-30Completed
Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease [NCT01001780]Phase 20 participants (Actual)Interventional2009-08-31Withdrawn(stopped due to Study stopped early due to poor accrual.)
Phase II Study to Evaluate the Safety and Efficacy of the Treatment With Pentostatin, Cyclophosphamide and Rituximab Followed by Rituximab Maintenance in Previously Untreated and Relapsed Patients With Immunocytoma/Morbus Waldenström, B-CLL and Other Indo [NCT00927797]Phase 2185 participants (Anticipated)Interventional2005-02-28Active, not recruiting
Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation [NCT00506922]Phase 1/Phase 2150 participants (Actual)Interventional2000-09-30Completed
A Phase I-II Study of Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Previously Treated Patients With Chronic Lymphocytic Leukemia and Other Low Grade B-Cell Neoplasms [NCT00546377]Phase 1/Phase 250 participants (Actual)Interventional2005-07-31Completed
A Phase I/II Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia [NCT00709215]Phase 1/Phase 244 participants (Anticipated)Interventional2008-06-30Recruiting
Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial [NCT00669318]Phase 241 participants (Actual)Interventional2008-07-31Completed
A Prospective, Randomized, Open Label, Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab vs. Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-cell Chronic Lymphocytic Leukemia [NCT00254163]Phase 3184 participants (Actual)Interventional2003-12-31Completed
Phase II Trial of Pentostatin, and Rituximab With and Without Cyclophosphamide for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) [NCT00201721]Phase 228 participants (Actual)Interventional2002-07-31Completed
Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Sickle Cell Disease Patients With COH-MC-17: a Non-Myeloablative, Conditioning Regimen and CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant [NCT03249831]Phase 13 participants (Actual)Interventional2019-01-04Active, not recruiting
Phase II Related or Unrelated Allogeneic Hematopoietic Cell Transplantation for High-Risk Malignancies, Using a Preparative Regimen of Pentostatin (Nipent®) and Alemtuzumab (Campath®) [NCT00698685]Phase 214 participants (Actual)Interventional2006-01-23Terminated(stopped due to Pentostatin/alemtuzumab regimen had greater risk of graft failure.)
Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies [NCT01188798]Phase 36 participants (Actual)Interventional2010-09-30Completed
Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab With or Without Concurrent Avastin® for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) [NCT00816595]Phase 268 participants (Actual)Interventional2009-02-28Completed
A Randomized Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation Versus Pentostatin and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies [NCT00402714]Phase 214 participants (Actual)Interventional2006-07-31Completed
Phase II Trial of Pentostatin in Steroid Refractory Acute Graft Versus Host Disease [NCT00201786]Phase 28 participants (Actual)Interventional2003-07-31Completed
Low Intensity Allogeneic Hematopoietic Stem Cell Transplantation Therapy of Metastatic Renal Cell Carcinoma Using Early and Multiple Donor Lymphocyte Infusions Consisting of Sirolimus-Generated Donor Th2 Cells [NCT00923845]Phase 225 participants (Actual)Interventional2008-03-01Completed
Non-Myeloablative Chemotherapy Followed By Related Allogeneic Stem Cell Rescue In Patients With Advanced Renal Cell Carcinoma [NCT00006968]Phase 1/Phase 24 participants (Actual)Interventional2000-09-30Completed
A Sequentially Adaptive, Open Label, Dose-finding, Phase I/II Trial of Pentostatin in the Treatment of Steroid-refractory Acute Graft Versus Host Disease (aGvHD) [NCT00032773]Phase 1/Phase 236 participants Interventional2002-01-30Terminated
A Phase II Study of Pentostatin For the Treatment of High Risk or Refractory Chronic GVHD in Children [NCT00144430]Phase 260 participants (Anticipated)Interventional2004-01-31Completed
A Phase II Study of Deoxycoformycin (DCF) in Lymphoid Malignancies [NCT00038025]Phase 260 participants (Actual)Interventional1994-09-06Completed
Pentostatin, Cyclophosphamide And Rituximab (PCR) For B-Cell Chronic Lymphocytic Leukemia (CLL) And Small B-Cell Lymphocytic Lymphoma (SLL): Four Phase II Trials With Patient Stratification Based On Prior Therapy [NCT00049413]Phase 20 participants Interventional2002-06-30Completed
Phase II Multicenter Trial Of Pentostatin and Rituximab In Patients With Previously Treated and Untreated Low Grade B-Cell Non-Hodgkin's Lymphoma (NHL) Including Chronic Lymphocytic Leukemia (CLL) [NCT00026351]Phase 20 participants Interventional2000-12-31Completed
A Phase II Study of Alemtuzumab and Pentostatin In T-Cell Neoplasms [NCT00453193]Phase 226 participants (Actual)Interventional2004-09-30Terminated(stopped due to Slow accrual.)
A Phase I-II Study of Pentostatin With Cyclophosphamide for Previously Treated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia [NCT00003658]Phase 260 participants (Anticipated)Interventional1998-09-30Completed
A Phase II Trial Of Intravenous Pentostatin For The Treatment Of Patients With Refractory Chronic Graft-Versus-Host Disease [NCT00074035]Phase 239 participants (Actual)Interventional2003-12-31Completed
Pentostatin and Donor Lymphocyte Infusion for Low Donor T-cell Chimerism After Hematopoietic Cell Transplantation - A Multi-center Trial [NCT00096161]Phase 236 participants (Actual)Interventional2003-05-31Completed
A Phase III Randomized Open-label Multi-center Study of Ruxolitinib vs. Best Available Therapy in Patients With Corticosteroid-refractory Chronic Graft vs Host Disease After Allogeneic Stem Cell Transplantation (REACH3) [NCT03112603]Phase 3330 participants (Actual)Interventional2017-06-29Completed
A Pilot/ Phase 2 Study of Pentostatin Plus Cyclophosphamide Immune Depletion to Decrease Immunogenicity of SS1P in Patients With Mesothelioma, Lung Cancer or Pancreatic Cancer [NCT01362790]Phase 1/Phase 255 participants (Actual)Interventional2011-05-11Completed
A Phase I Study of Cordycepin (NSC 63984) Plus 2'-Deoxycoformycin (NSC 218321) in Patients With Refractory TdT-Positive Leukemia [NCT00003005]Phase 114 participants (Actual)Interventional1997-12-31Completed
Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia [NCT01059786]Phase 268 participants (Actual)Interventional2010-07-01Active, not recruiting
Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Campath-1H for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia [NCT00074282]Phase 2102 participants (Actual)Interventional2005-04-14Completed
A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplantation for the Treatment of Relapsed Non-Hodgkin and Hodgkin Lymphoma [NCT00057954]Phase 26 participants (Actual)Interventional2005-11-09Terminated(stopped due to Slow accrual)
A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes [NCT00045305]Phase 217 participants (Actual)Interventional2006-10-24Completed
T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation [NCT00816413]Phase 1/Phase 20 participants (Actual)Interventional2008-09-30Withdrawn(stopped due to Screenings yielded inadequate eligible subjects to enroll.)
Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) [NCT01024010]Phase 282 participants (Actual)Interventional2010-03-31Completed
Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab Followed by Consolidation With Lenalidomide for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) [NCT00602836]Phase 245 participants (Actual)Interventional2008-02-29Completed
Phase II Trial of Pentostatin and Targeted Busulfan as a Novel Reduced Intensity Regimen for Allogeneic Hematopoietic Stem Cell Transplantation Using Laboratory-Guided (CD4-guided) Immunosuppression. [NCT00496340]Phase 242 participants (Actual)Interventional2007-07-31Completed
Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease [NCT03077542]Phase 1/Phase 255 participants (Actual)Interventional2017-04-06Active, not recruiting
Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia in Individuals With Higher Risk of Transplant Failure [NCT02105766]Phase 2162 participants (Anticipated)Interventional2014-04-21Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00045305 (6) [back to overview]Number of Patients Who Developed Disease Progression After Achieving Complete Response
NCT00045305 (6) [back to overview]Time to Engraftment for Platelet
NCT00045305 (6) [back to overview]Proportion of Graft Versus Host Disease
NCT00045305 (6) [back to overview]Overall Survival
NCT00045305 (6) [back to overview]Time to Engraftment for Neutrophil
NCT00045305 (6) [back to overview]Complete Response Rate
NCT00057954 (3) [back to overview]Progression-free Survival
NCT00057954 (3) [back to overview]100-day Overall Survival
NCT00057954 (3) [back to overview]Proportion of Participants With Successful Engraftment
NCT00074035 (4) [back to overview]Overall Survival At 2 Years
NCT00074035 (4) [back to overview]Response Rate
NCT00074035 (4) [back to overview]Grade 3 or Higher Non-hematologic Adverse Events
NCT00074035 (4) [back to overview]Overall Survival At 1 Year
NCT00074282 (5) [back to overview]Response Rate
NCT00074282 (5) [back to overview]Overall Survival (OS)
NCT00074282 (5) [back to overview]Number of Patients Who After PCR (or During PCR for PD), Only Achieve a PR, SD, or PD and Who Subsequently Convert to a Higher Response Category After Campath-1H
NCT00074282 (5) [back to overview]Molecular Complete Remission (MCR) Rate
NCT00074282 (5) [back to overview]Progression-free Survival (PFS)
NCT00096161 (6) [back to overview]Incidence of Grade IV Acute GVHD
NCT00096161 (6) [back to overview]Incidence of Infections
NCT00096161 (6) [back to overview]Incidence of Relapse/Progression
NCT00096161 (6) [back to overview]Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism
NCT00096161 (6) [back to overview]Survival
NCT00096161 (6) [back to overview]Incidence of GVHD
NCT00224874 (8) [back to overview]Number of Complete Response (CR) at Day 28 of Therapy
NCT00224874 (8) [back to overview]Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90
NCT00224874 (8) [back to overview]Number of Patients With Chronic Graft-versus-host Disease (GVHD)
NCT00224874 (8) [back to overview]Proportion of Treatment Failure
NCT00224874 (8) [back to overview]Number of Patients Discontinuing Immune Suppression Without Flare
NCT00224874 (8) [back to overview]Number of Partial Response (PR), Mixed Response (MR), and Progression
NCT00224874 (8) [back to overview]Cumulative Incidence of Systemic Infections
NCT00224874 (8) [back to overview]Number of Patients Surviving at 6 and 9 Months Post Randomization
NCT00254163 (9) [back to overview]Complete Remission (CR)
NCT00254163 (9) [back to overview]Hematologic Recovery
NCT00254163 (9) [back to overview]Infection Rate
NCT00254163 (9) [back to overview]Infective Event Rate
NCT00254163 (9) [back to overview]Mean Absolute Neutrophil Count (ANC) at Post-treatment
NCT00254163 (9) [back to overview]Objective Remission Rate (ORR)
NCT00254163 (9) [back to overview]Percentage of Patients Hospitalized
NCT00254163 (9) [back to overview]Progression-free Survival (PFS) Rate at 1-year
NCT00254163 (9) [back to overview]Progression-free Survival (PFS) Rate at 2-year
NCT00402714 (2) [back to overview]Overall Survival
NCT00402714 (2) [back to overview]Incidence of Grade 2-4 Acute Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation in Patients Randomized to Photopheresis vs. no Photopheresis
NCT00453193 (1) [back to overview]Number of Participants With Objective Response
NCT00496340 (10) [back to overview]Non-relapse Mortality Rate (NRM)
NCT00496340 (10) [back to overview]Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +100
NCT00496340 (10) [back to overview]Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +28
NCT00496340 (10) [back to overview]Time to Incidence of Graft Versus Host Disease (GVHD)
NCT00496340 (10) [back to overview]Cumulative Incidence of Hematopoietic Cell Engraftment
NCT00496340 (10) [back to overview]Incidence of Greater Than or Equal to 50% Donor Chimerism
NCT00496340 (10) [back to overview]Percentage of Participants With Overall Survival (OS)
NCT00496340 (10) [back to overview]Percentage of Participants With Progression Free Survival (PFS)
NCT00496340 (10) [back to overview]Incidence of Graft Versus Host Disease (GVHD)
NCT00496340 (10) [back to overview]Incidence of Infections
NCT00496873 (3) [back to overview]3-Year Progression-Free Survival
NCT00496873 (3) [back to overview]Number of Participants With Complete Response (CR)/Complete Response Unconfirmed (CRu) With Low-grade Lymphoma (N=83) After 6-9 Cycles of PCR Therapy
NCT00496873 (3) [back to overview]Participant Response Rate According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999
NCT00506922 (1) [back to overview]Number of Patients Without GVHD at 100 Days
NCT00546377 (2) [back to overview]Maximum Tolerated Dose (MTD) of Mitoxantrone
NCT00546377 (2) [back to overview]Overall Response
NCT00571662 (5) [back to overview]Kinetics of Immunologic Reconstitution
NCT00571662 (5) [back to overview]Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting
NCT00571662 (5) [back to overview]Responses to Therapy
NCT00571662 (5) [back to overview]Toxicity for the Combination of Pentostatin and Low Dose Total Body Irradiation (TBI)
NCT00571662 (5) [back to overview]Incidence of Acute and Chronic Graft-versus-host Disease
NCT00602836 (6) [back to overview]Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide
NCT00602836 (6) [back to overview]Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide
NCT00602836 (6) [back to overview]Treatment Free Survival (TFS)
NCT00602836 (6) [back to overview]Overall Survival (OS)
NCT00602836 (6) [back to overview]Number of Participants With a Response (CR, nPR, PR)
NCT00602836 (6) [back to overview]Number of Participants With Complete Response (CR)
NCT00669318 (5) [back to overview]Complete Response Rate
NCT00669318 (5) [back to overview]Overall Response Rate (Complete and Partial Response)
NCT00669318 (5) [back to overview]Overall Survival
NCT00669318 (5) [back to overview]Progression-free Survival
NCT00669318 (5) [back to overview]Time to Retreatment
NCT00698685 (2) [back to overview]Actuarial Probability of Donor Hematopoietic Engraftment (Defined as at Least 50% Donor DNA in Bone Marrow at Day 100).
NCT00698685 (2) [back to overview]Non-relapse Mortality at or Before Day 100
NCT00816595 (3) [back to overview]Overall Survival
NCT00816595 (3) [back to overview]Progression-free Survival
NCT00816595 (3) [back to overview]Complete and Overall Response Rate
NCT00923845 (16) [back to overview]Count of Patients With Chronic Graft Versus Host Disease (GVHD)
NCT00923845 (16) [back to overview]Count of Patients With Grade II or Greater Acute Graft Versus Host Disease (GVHD) in First 100 Days Post-Transplant
NCT00923845 (16) [back to overview]Count of Patients With Late Acute Graft Versus Host Disease (GVHD) After Day 100 Post-Transplant
NCT00923845 (16) [back to overview]Immune Depletion in Cluster of Differentiation 4 (CD4) Cells
NCT00923845 (16) [back to overview]Clinical Regression of Metastatic Renal Cell Carcinoma (Partial Response (PR)) or Complete Remission of Tumor (Complete Response (CR))
NCT00923845 (16) [back to overview]Count of Patients Having an Infectious Complication Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen
NCT00923845 (16) [back to overview]Cluster of Differentiation 8 (CD8)+ T Cells Immune Reconstitution
NCT00923845 (16) [back to overview]Engraftment Donor T Cell and Myeloid Cell Chimerism
NCT00923845 (16) [back to overview]Immune Depletion in Cluster of Differentiation 8 (CD8)+ T Cells
NCT00923845 (16) [back to overview]Immune Suppression
NCT00923845 (16) [back to overview]Cluster of Differentiation 4 (CD4) T Cells Immune Reconstitution
NCT00923845 (16) [back to overview]Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th1 Transcription Factor T-bet
NCT00923845 (16) [back to overview]Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th2 Transcription Factor GATA Binding Protein 3 (GATA-3)
NCT00923845 (16) [back to overview]Count of Participants With Adverse Events
NCT00923845 (16) [back to overview]Count of Patients Having Neutropenia Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen
NCT00923845 (16) [back to overview]Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the T-reg Transcription Factor Forkhead Box P3 (FoxP3))
NCT01024010 (5) [back to overview]Overall Response Rate
NCT01024010 (5) [back to overview]Arm A: Percentage of Complete Responses
NCT01024010 (5) [back to overview]Arm B: Treatment-free Survival at 18 Months
NCT01024010 (5) [back to overview]Depth of Response After Ofatumumab Consolidation
NCT01024010 (5) [back to overview]Treatment-free Survival
NCT01362790 (8) [back to overview]Progression-free Survival
NCT01362790 (8) [back to overview]Recommended Phase 2 Dose (RP2D) in Drug Lot FIL129J01
NCT01362790 (8) [back to overview]Count of Participants SS1P Cycles Received Following Onstudy
NCT01362790 (8) [back to overview]Response Assessment
NCT01362790 (8) [back to overview]Duration of Response
NCT01362790 (8) [back to overview]Count of Participants With SS1P Antibody Formation
NCT01362790 (8) [back to overview]Overall Survival
NCT01362790 (8) [back to overview]Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered SS1P and Pentostatin or Cyclophosphamide
NCT03112603 (24) [back to overview]Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Cumulative Incidence of Malignancy Relapse/Recurrence (MR)
NCT03112603 (24) [back to overview]t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose
NCT03112603 (24) [back to overview]Percentage of Participants Successfully Tapered Off of All Corticosteroids
NCT03112603 (24) [back to overview]Cumulative Incidence of Non-relapse Mortality (NRM)
NCT03112603 (24) [back to overview]Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)
NCT03112603 (24) [back to overview]Change From Baseline in EQ-5D-5L
NCT03112603 (24) [back to overview]AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Best Overall Response (BOR) at Cycle 7 Day 1
NCT03112603 (24) [back to overview]AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
NCT03112603 (24) [back to overview]Utilization of Medical Resources
NCT03112603 (24) [back to overview]BOR During Cross-over Treatment With Ruxolitinib
NCT03112603 (24) [back to overview]Duration of Response Through Study Completion
NCT03112603 (24) [back to overview]Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit
NCT03112603 (24) [back to overview]Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
NCT03112603 (24) [back to overview]ORR at the End of Cycle 3
NCT03112603 (24) [back to overview]Overall Survival (OS)
NCT03112603 (24) [back to overview]Rate of Failure-free Survival (FFS)
NCT03112603 (24) [back to overview]Rate of FFS at Study Completion
NCT03112603 (24) [back to overview]Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score

Number of Patients Who Developed Disease Progression After Achieving Complete Response

Disease free survival (DFS) was listed as a secondary endpoint in the study protocol, which would be assessed in patients who achieved complete response (CR). It was defined to be time from CR to documented progression or to death without progression. Patients without documented progression or death reported were censored at the time of last disease evaluation. However, due to the small number of patients with CR, the number of patients who developed disease progression was reported here. (NCT00045305)
Timeframe: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Interventionparticipants (Number)
Arm I1

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Time to Engraftment for Platelet

Time to platelet engraftment is defined from date of infusion to date of platelet engraftment. The platelet engraftment is defined as platelets > 20,000 on two consecutive measurements, at least seven days apart, without platelet transfusions in between and for at least three days before the first measurement that is over 20,000. The date of engraftment is the date of the first measurement that is over 20,000. (NCT00045305)
Timeframe: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

Interventiondays (Median)
Arm I18

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Proportion of Graft Versus Host Disease

Proportion of Graft versus Host Disease is calculated as number of patients with Graft versus Host Disease divided by all eligible and treated patients (NCT00045305)
Timeframe: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Interventionproportion of participants (Number)
Arm I0.412

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Overall Survival

Overall survival (OS) is defined to be the time from registration to death from any cause, with follow-up censored at the date of last contact. Kaplan-Meier method was used to estimate the distribution of OS. (NCT00045305)
Timeframe: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Interventionyears (Median)
Arm I1.2

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Time to Engraftment for Neutrophil

Time to neutrophil engraftment is defined from date of infusion to date of neutrophil engraftment. Neutrophil engraftment is defined as ANC > 500/mm3 on two consecutive measurements. The date of engraftment is the date of the first ANC > 500/mm3. (NCT00045305)
Timeframe: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

Interventiondays (Median)
Arm I18

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Complete Response Rate

"Completed response is defined as:~Bone marrow evaluation: Repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation).~Peripheral blood evaluation [absolute values must last at least 2 months] Hemoglobin >11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present" (NCT00045305)
Timeframe: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Interventionpercentage of participants (Number)
Arm I35.3

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Progression-free Survival

Progression-free survival was defined as time from enrollment to disease progression or death from any cause, whichever occurred first. Patients who did not have progression-free survival events were censored at last date of disease assessment. (NCT00057954)
Timeframe: Assessed day 100 post transplant and every 3 months during year 1, every 6 months during years 2-3, then every 12 months during years 4-5 or through diagnosis of disease progression

Interventiondays (Median)
Transplant104

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100-day Overall Survival

Proportion of patients who survived 100 days or more after enrolled on the study (NCT00057954)
Timeframe: Assessed at least twice a week for the first 60 days and weekly until day 100.

InterventionProportion of participants (Number)
Transplant0.83

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Proportion of Participants With Successful Engraftment

(NCT00057954)
Timeframe: Assessed daily during inpatient stay

InterventionProportion of participants (Number)
Transplant1

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Overall Survival At 2 Years

Percentage of patients who were alive at 2 years. (NCT00074035)
Timeframe: 2 year

Interventionpercentage of participants (Number)
Pentostatin50

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Response Rate

"Percentage of participants who had a complete or partial response defined by the Hopkins scoring system.~A complete response is defined as the disappearance of signs and symptoms of chronic GVHD in all involved systems that is sustained for at lest 4 weeks. A partial response is an improvement by 2 or more points in at least one system score, which is sustained for at least 4 weeks, with no signs of worsening in others." (NCT00074035)
Timeframe: 3 months

Interventionpercentage of participants (Number)
Pentostatin20

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Grade 3 or Higher Non-hematologic Adverse Events

Number of participants experiencing a grade 3, 4 or 5 clinically significant non-hematologic adverse events, at least possibly related to treatment. (NCT00074035)
Timeframe: Duration of treatment (up to 5 years)

Interventioncount of participants (Number)
FatigueRenal failureAnorexiaInfectionCNS hemmorrhageRashPersonality/behavioralPneumonitis
Pentostatin342101111

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Overall Survival At 1 Year

Percentage of patients who were alive at 1 year. (NCT00074035)
Timeframe: 1 year

Interventionpercentage of participants (Number)
Pentostatin53

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Response Rate

Percent with response (CR, nPR, PR) with two-stage 90% confidence interval (NCT00074282)
Timeframe: 8 weeks after Cycle 6

Interventionpercentage (Number)
Arm A (PCR)55.2

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Overall Survival (OS)

OS is defined as the time from registration until death from any cause. (NCT00074282)
Timeframe: Up to 5 years from registration

Interventionmonths (Median)
Arm A (PCR)27.6

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Number of Patients Who After PCR (or During PCR for PD), Only Achieve a PR, SD, or PD and Who Subsequently Convert to a Higher Response Category After Campath-1H

(NCT00074282)
Timeframe: From re-registration up to 5 years (followed for response until progression)

InterventionParticipants (Count of Participants)
Arm C (Alemtuzumab: PR, 4

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Molecular Complete Remission (MCR) Rate

Percent of patients who have MCR (clinical CR with flow negative and RT-PCR negative) (NCT00074282)
Timeframe: 3 months post alemtuzumab

Interventionpercentage (Number)
Arm B (Alemtuzumab: CR, nPR)44.4

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Progression-free Survival (PFS)

PFS is defined as the time from registration until induction failure, institution of non-protocol therapy, relapse or death from any cause in the absence of relapse. (NCT00074282)
Timeframe: Up to 5 years from registration

Interventionmonths (Median)
Arm A (PCR)12.2

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Incidence of Grade IV Acute GVHD

"Clinical Stage of acute GVHD according to Organ System~Skin:~- Maculopapular rash <25% of body surface~- Maculopapular rash 25-50% of body surface~- Maculopapular rash >50% body surface area or generalized erythroderma~- Generalized erythroderma with bullous formation and desquamation~Liver:~- Bilirubin 2-3 mg/dl~- Bilirubin 3.1-6 mg/dl~- Bilirubin 6.1-15 mg/dl~- Bilirubin >15 mg/dl~Gut:~- >500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD~- >1000 -1500 mL diarrhea per day~- >1500 mL diarrhea per day~- >1500 mL diarrhea per day plus severe abdominal pain with or without ileus~Overall Clinical Grading of Severity of acute GVHD Grade IV: 0-4 Skin, 2-4 Liver, and/or 2-4 GI" (NCT00096161)
Timeframe: Within 100 days after the last DLI

Interventionpercentage of participants (Number)
Group 1A (Pentostatin, DLI Dose Level 1)5
Group 1B (Pentostatin, DLI Dose Level 2)0
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)0

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Incidence of Infections

(NCT00096161)
Timeframe: 100 days after DLI

Interventionpercentage of participants (Number)
Group 1A (Pentostatin, DLI Dose Level 1)80
Group 1B (Pentostatin, DLI Dose Level 2)70
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)33.3

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Incidence of Relapse/Progression

"CML Acquisition of a new cytogenetic abnormality and/or development of accelerated phase or blast crisis. Criteria for accelerated phase: unexplained fever >38.3° C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, BM blasts and promyelocytes >20%.~AML, ALL, CMML >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia.~CLL Progressive disease: ≥1 of: physical exam/imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation.~NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions.~MM~≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ tx; or definite increase in the size/number of plasmacytomas or lytic bone lesions." (NCT00096161)
Timeframe: 1 year after DLI

Interventionpercentage of participants (Number)
Group 1A (Pentostatin, DLI Dose Level 1)45
Group 1B (Pentostatin, DLI Dose Level 2)20
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)33.3

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Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism

"A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then it can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements.~Chimerism in hematopoietic cell transplant derives from this idea of a mixed entity, referring to someone who has received a transplant of genetically different tissue. A test for chimerism after a hematopoietic cell transplant involves identifying the genetic profiles of the recipient and of the donor and then evaluating the extent of mixture in the recipient's blood cells or marrow cells." (NCT00096161)
Timeframe: From the time of enrollment maintained to day 56 after the last DLI, up to Day 112

Interventionpercentage of participants (Number)
Group 1A (Pentostatin, DLI Dose Level 1)60
Group 1B (Pentostatin, DLI Dose Level 2)30
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)33.3

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Survival

Percentage patients surviving. (NCT00096161)
Timeframe: 1 year after DLI

Interventionpercentage of participants (Number)
Group 1A (Pentostatin, DLI Dose Level 1)60
Group 1B (Pentostatin, DLI Dose Level 2)90
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)66.7

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Incidence of GVHD

"Percentage patients with acute or chronic GVHD.~The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD." (NCT00096161)
Timeframe: 1 year after DLI

,,
Interventionpercentage of participants (Number)
aGVHDcGVHD
Group 1A (Pentostatin, DLI Dose Level 1)2050
Group 1B (Pentostatin, DLI Dose Level 2)020
Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)016.7

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Number of Complete Response (CR) at Day 28 of Therapy

Complete response at day 28 after randomization. CR was defined as resolution of all signs and symptoms of Graft-Versus-Host Disease (GVHD) in all evaluable organs in comparison to Day 1 scoring. (NCT00224874)
Timeframe: Measured at Day 28

Interventionparticipants (Number)
Etanercept12
Mycophenolate Mofetil27
Denileukin Diftitox25
Pentostatin16

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Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90

Flares were defined as any increase in symptoms of or therapy for acute GVHD after an initial response (i.e., progression from an earlier CR or PR). (NCT00224874)
Timeframe: Measured at Day 90

Interventionparticipants (Number)
Etanercept16
Mycophenolate Mofetil12
Denileukin Diftitox15
Pentostatin15

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Number of Patients With Chronic Graft-versus-host Disease (GVHD)

Number of patients with limited and extensive chronic GVHD at 9 months (NCT00224874)
Timeframe: Measured at 9 months

Interventionparticipants (Number)
Etanercept11
Mycophenolate Mofetil19
Denileukin Diftitox15
Pentostatin12

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Proportion of Treatment Failure

(NCT00224874)
Timeframe: Measured at Day 56

Interventionpercentage of participants (Number)
Etanercept24
Mycophenolate Mofetil9
Denileukin Diftitox26
Pentostatin29

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Number of Patients Discontinuing Immune Suppression Without Flare

Immunosuppression discontinuation was defined as the discontinuation of corticosteroids and all additional immunosuppressives, except cyclosporine or tacrolimus, for treatment of acute GVHD without subsequent flare by Day 90 post-initiation of therapy and later by discontinuation of all immunosuppressive medications, including cyclosporine or tacrolimus. (NCT00224874)
Timeframe: Measured at Days 90, 180, and 270 post-treatment

,,,
Interventionparticipants (Number)
Day 90Day 180Day 270
Denileukin Diftitox5810
Etanercept71216
Mycophenolate Mofetil41317
Pentostatin2810

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Number of Partial Response (PR), Mixed Response (MR), and Progression

Partial response, mixed response, and progression at Day 28 after randomization. Partial response was defined as improvement in one or more organs involved with Graft-Versus-Host Disease (GVHD) symptoms without progression in others. Mixed response was defined as improvement in one or more organs with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. Progression was defined as deterioration in at least one organ without any improvement in others. (NCT00224874)
Timeframe: Measured at Day 28

,,,
Interventionparticipants (Number)
Partial ResponseMixed ResponseProgression
Denileukin Diftitox303
Etanercept1037
Mycophenolate Mofetil841
Pentostatin1024

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Cumulative Incidence of Systemic Infections

(NCT00224874)
Timeframe: Measured at Day 270

Interventionpercentage of participants (Number)
Etanercept47
Mycophenolate Mofetil44
Denileukin Diftitox62
Pentostatin57

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Number of Patients Surviving at 6 and 9 Months Post Randomization

(NCT00224874)
Timeframe: Measured at 6 and 9 months

,,,
Interventionparticipants (Number)
Month 6Month 9
Denileukin Diftitox2824
Etanercept2622
Mycophenolate Mofetil3229
Pentostatin2421

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Complete Remission (CR)

"Definitions of response is evaluated using guidelines proposed by the National Cancer Institute-Sponsored Working Group for Chronic Lymphocytic Leukemia.~Complete remission (CR) requires all of the following for a period of at least 2 months:~Absence of lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must be <1 cm.~No evidence of hepatomegaly or splenomegaly.~Absence of constitutional symptoms.~Normal CBC as exhibited by:~Polymorphonuclear leukocytes ≥ 1,500/mm^3~Platelets > 100,000/mm^3~Hemoglobin > 11.0 g/dL (untransfused)~Bone marrow aspirate and biopsy should be performed 2 months after clinical and laboratory results demonstrate that all of the requirements listed in 1-4 have been met to demonstrate that a CR has been achieved. The marrow sample must be at least normocellular for age, with less than 30% of the nucleated cells being lymphocytes.~Lymphoid nodules should be absent." (NCT00254163)
Timeframe: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Interventionpercentage of participants (Number)
FCR Arm14.0
PCR Arm7.1

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Hematologic Recovery

defined as Hb >11g/dL and a platelet count >100 × 10^3/mm^3 (NCT00254163)
Timeframe: 2 months post-treatment

Interventionpercentage of participants (Number)
FCR Arm3.5
PCR Arm14.1

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Infection Rate

infection=febrile events requiring treatment (NCT00254163)
Timeframe: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Interventionpercentage of participants (Number)
FCR Arm31.4
PCR Arm36.5

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Infective Event Rate

infective events=temperature >101 without symptoms or temp <101 with symptoms (NCT00254163)
Timeframe: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Interventionpercentage of infective events (Number)
FCR Arm38
PCR Arm45

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Mean Absolute Neutrophil Count (ANC) at Post-treatment

mean Absolute Neutrophil Count (ANC) measured 2 months (8-10 weeks) following the last dose of study treatment (NCT00254163)
Timeframe: 2 months post-treatment

Intervention10^3 cells/mm^3 (Mean)
FCR Arm1.7
PCR Arm2.2

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Objective Remission Rate (ORR)

"Complete remission (CR) see Outcome Measure 6. Partial remission (PR) must exhibit criteria 1 and 2 as well as one or more of the remaining features for at least 2 months.~≥50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value.~≥50% reduction in lymphadenopathy.~≥50% reduction in the size of the liver and/or spleen.~Polymorphonuclear leukocytes ≥ 1,500/mm^3 or 50% improvement over baseline.~Platelets >100,000/mm^3 or 50% improvement over baseline.~Hemoglobin >11.0 g/dL or 50% improvement over baseline without transfusions. Nodular partial remission (nPR) is defined as a CR with persistent bone marrow nodules; Objective Remission (OR) = CR + PR + nPR." (NCT00254163)
Timeframe: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Interventionpercentage of participants (Number)
FCR Arm59.3
PCR Arm49.4

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Percentage of Patients Hospitalized

Percentage of patients who were hospitalized due to any reasons during the study period. (NCT00254163)
Timeframe: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Interventionpercentage of participants (Number)
FCR Arm35
PCR Arm43.5

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Progression-free Survival (PFS) Rate at 1-year

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date (NCT00254163)
Timeframe: 12 months after registered.

Interventionprobability of Progression-free Survival (Number)
FCR Arm0.86
PCR Arm0.84

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Progression-free Survival (PFS) Rate at 2-year

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. (NCT00254163)
Timeframe: 24 months after registered.

InterventionProbability of Progression-free Survival (Number)
FCR Arm0.72
PCR Arm0.63

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Overall Survival

(NCT00402714)
Timeframe: 2 years following stem cell transplant

Interventionparticipants (Number)
ECP Pento TBI2
Pento TBI5

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Incidence of Grade 2-4 Acute Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation in Patients Randomized to Photopheresis vs. no Photopheresis

(NCT00402714)
Timeframe: Day +100 following allogeneic stem cell transplant

Interventionparticipants (Number)
1 ECP and Pent/TBI1
2 Pent/TBI8

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Number of Participants With Objective Response

Objective Responses are Complete or Partial Responses: Complete Response defined as disappearance of all evidence of disease detectable by morphology of peripheral blood and bone marrow and computer tomography scanning at the end of therapy, if indicated; and Partial Response as 50% or more reduction in detectable disease, but short of complete response, maintained for 1 month or at least 50% reduction of sum of the products of the diameter of all lesions for 1 month. (NCT00453193)
Timeframe: After a maximum of 6 months of therapy maintained for one month.

InterventionParticipants (Number)
Complete ResponsePartial Response
Alemtuzumab + Pentostatin112

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Non-relapse Mortality Rate (NRM)

The cumulative incidence of NRM after allo-HCT. (NCT00496340)
Timeframe: Up to 2 years post-transplant

Interventionpercentage of participants (Number)
Day +1002 Years
Conditioning Followed by HCT217

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Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +100

Median Percentage of Donor Cells in Study Population (Chimerism). (NCT00496340)
Timeframe: 100 days post-transplant

Interventionpercentage of cells (Median)
CD3+CD33+
Conditioning Followed by HCT96100

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Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +28

Median Percentage of Donor Cells in Study Population (Chimerism). (NCT00496340)
Timeframe: 28 days post-transplant

Interventionpercentage of cells (Median)
CD3+CD33+
Conditioning Followed by HCT87100

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Time to Incidence of Graft Versus Host Disease (GVHD)

"The median time from allo-HCT to the initiation of tacrolimus (TAC) taper.~The median time to onset of acute GVHD (aGVHD). Clinical manifestations of acute GVHD include a classic maculopapular rash; persistent nausea and/or emesis; abdominal cramps with diarrhea; and a rising serum bilirubin concentration." (NCT00496340)
Timeframe: Up to 2 years post-transplant

Interventiondays (Median)
Initiation of TAC TaperOnset of aGVHD
Conditioning Followed by HCT6233

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Cumulative Incidence of Hematopoietic Cell Engraftment

Hematologic engraftment: defined as time to achieve an absolute neutrophil count (ANC) >/= 500/µl for 3 consecutive days or a platelet count of >/= 20,000//µl without the need for platelet support. (NCT00496340)
Timeframe: 28 days post-transplant

Interventionpercentage of participants (Number)
Conditioning Followed by HCT97.6

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Incidence of Greater Than or Equal to 50% Donor Chimerism

The primary endpoint was achievement of >/= 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7) after allogeneic hematopoietic cell transplantation (allo-HCT). (NCT00496340)
Timeframe: 28 days post-transplant

Interventionpercentage of participants (Number)
Conditioning Followed by HCT100

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Percentage of Participants With Overall Survival (OS)

OS at 2 years post-transplant. OS, defined as time from day of hematopoietic cell infusion to death from any cause. (NCT00496340)
Timeframe: 2 years post-transplant

Interventionpercentage of participants (Number)
Conditioning Followed by HCT68

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Percentage of Participants With Progression Free Survival (PFS)

PFS at 2 years post-transplant. PFS, defined as time from day of hematopoietic cell infusion to disease relapse. Relapsed disease: Disease was in complete remission post-transplant but returned (e.g., >5% blast in bone marrow or any peripheral blasts). (NCT00496340)
Timeframe: 2 years post-transplant

Interventionpercentage of participants (Number)
Conditioning Followed by HCT55

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Incidence of Graft Versus Host Disease (GVHD)

"By day +100, the cumulative incidence of GVHD, acute of grades 2-4, and 3-4.~At 2 years, the cumulative incidence of chronic GVHD of any severity according to National Institutes of Health (NIH) consensus criteria. Diagnosis of chronic GVHD requires the presence of at least one diagnostic clinical sign of chronic GVHD or the presence of at least one distinctive manifestation confirmed by pertinent biopsy or other relevant tests in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD.~At 2 years, the cumulative incidence of moderate/severe chronic GVHD." (NCT00496340)
Timeframe: Up to 2 years post-transplant

Interventionpercentage of participants (Number)
Day +100 aGVHD Grade 2-4Day +100 aGVHD Grade 3-42 Years, Chronic GVHD of Any Severity2 Years, Moderate/Severe Chronic GVHD
Conditioning Followed by HCT59196958

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Incidence of Infections

Infections: Incidence of infections (opportunistic and non-opportunistic) following conditioning. (NCT00496340)
Timeframe: Up to 2 years post-transplant

Interventionparticipants (Number)
Cytomegalovirus (CMV) ReactivationEpstein-Barr virus (EBV) ReactivationPost-transplantation Lymphoproliferative DisorderViral InfectionsLung Infections
Conditioning Followed by HCT173152

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3-Year Progression-Free Survival

Progression-free survival (PFS) was defined as time from initiation of therapy to progression of disease or death, whichever occurred first. The Kaplan-Meier method was used to estimate PFS. (NCT00496873)
Timeframe: PFS assessed 7 days prior to every cycle and then every 3 months after off-treatment for one year, every 6 months for second year, then once on third year

Interventionpercentage of participants (Number)
Cytoxan + Rituxan + Nipent73

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Number of Participants With Complete Response (CR)/Complete Response Unconfirmed (CRu) With Low-grade Lymphoma (N=83) After 6-9 Cycles of PCR Therapy

Number of participants with response according to the International Working Group (IWG) anatomic criteria for assessing six categories of efficacy response or nonresponse to treatment in non-Hodgkins lymphoma (NHL): complete remission (CR), complete remission/unconfirmed (CRu), partial remission (PR), stable disease (SD), relapsed disease (RD), and progressive disease (PD). Response was assessed after 3, 6, and 9 cycles of therapy. (NCT00496873)
Timeframe: 9 cycles of 21 days, up to 7 months

Interventionparticipants (Number)
Cytoxan + Rituxan + Nipent72

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Participant Response Rate According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999

Number of participants with response out of total treated participants using IWG defined 6 categories based on IWG 1999 Response Criteria for NHL of efficacy response or nonresponse to treatment in non-Hodgkins lymphoma (NHL): complete remission (CR), complete remission/unconfirmed (CRu), partial remission (PR), stable disease (SD). CR: is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. PR: is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions. SD: participants who have achieved less than a PR but who have not developed findings consistent with progressive disease. (NCT00496873)
Timeframe: Evaluated after treatment in Cycles 3, 6 and 9 (1 Cycle = 21 Days), up to 7 months

InterventionPercentage of Participants (Number)
CR/CRuOverall response
Cytoxan + Rituxan + Nipent86.891.6

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Number of Patients Without GVHD at 100 Days

The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days. (NCT00506922)
Timeframe: 100 days

Interventionparticipants (Number)
Pentostatin100

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Maximum Tolerated Dose (MTD) of Mitoxantrone

The MTD is defined as the highest dose studied for which the incidence of DLT is less than 33%. In the phase I portion of the trial, cohorts of 3-6 pts will receive pentostatin, cyclophosphamide and rituximab along with one of three potential dose levels of mitoxantrone. The following dose escalation scheme will be followed: If none of the initial three pts in a cohort experience a dose-limiting toxicity (grade 4 infection, or grade ≥ 3 non-hematologic toxicity that persists for 7 days or more) then a new cohort of three pts will be treated at the next higher dose level. If one of the three pts in a cohort experiences DLT, then up to three additional pts will be treated at the same dose level. If two or more pts in a cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. The previous dose level will be considered as the MTD. (NCT00546377)
Timeframe: 2 years

Interventionmg/m2 (Number)
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone10

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Overall Response

Complete response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment): it is recognized that some patients with lymphoid malignancies who achieve a CR may have mild persistent abnormalities on CT Scan. Such abnormalities if stable on subsequent scanning will not be viewed as persistent disease in patients who otherwise meet the criteria for CR. Response will be assessed on an ongoing basis, but at a minimum of prior to cycle four and following completion of all therapy. Patients who are removed from study early will have response status determined at time of removal from study. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response. (NCT00546377)
Timeframe: 3 years

Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgression of Disease
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone112345

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Kinetics of Immunologic Reconstitution

Rate of return of immune cells after allogeneic transplantation (NCT00571662)
Timeframe: at day 100 post transplantation

,
Interventionpercentage of cells in peripheral blood (Median)
CD3 cellsCD4 cellsCD8 cells
Day + 28 Post Transplant73.51.7
Study Baseline1355

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Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting

the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70. (NCT00571662)
Timeframe: days +28 and +70

Interventionpercent of participants (Median)
Day 28Day 70
Cohort I8590

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Responses to Therapy

event-free and overall survival at 12 months (NCT00571662)
Timeframe: every 6 mo. up to 2 years

InterventionPercent of Participants (Number)
Event free survivalOverall survival
Cohort I5259

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Toxicity for the Combination of Pentostatin and Low Dose Total Body Irradiation (TBI)

(NCT00571662)
Timeframe: Conditioning regimen to count recovery (D + 28 post transplant)

InterventionParticipants (Count of Participants)
Absolute neutrophil count < 500/mm^3platelet count < 20,000/mm^3Grade 3 or 4 FeverGrade 3 or 4 hypokalemiaGrade 3 or 4 bacteremiaGrade 3 or 4 infectionGrade 3 or 4 renal toxicityGrade 3 or 4 thromboembolism
Cohort I4029212611

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Incidence of Acute and Chronic Graft-versus-host Disease

Incidence of acute and chronic graft-versus-host disease. Acute GVHD usually occurs during the first three months following transplant. Chronic GVHD usually develops after the third month post-transplant. (NCT00571662)
Timeframe: twice weekly until day 100 up to 1 year post transplant

InterventionPercent of Particpants (Number)
Acute GVHDChronic GVHD
Cohort I3133

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Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide

"According to the NCIWG criteria, response is defined as follows:~nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above" (NCT00602836)
Timeframe: 12 months

InterventionParticipants (Count of Participants)
PCR-Lenalidomide5

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Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide

MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD. (NCT00602836)
Timeframe: 12 months

InterventionParticipants (Count of Participants)
PCR-Lenalidomide4

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Treatment Free Survival (TFS)

Treatment Free Survival (TFS) was defined as the time from registration to the earliest date documentation of subsequent treatment or death, whichever came first. Participants were followed for a maximum of 5 years from registration. The median TFS with 95% CI was estimated using the Kaplan Meier method. (NCT00602836)
Timeframe: time from registration to progression (up to 5 years)

Interventionmonths (Median)
PCR-LenalidomideNA

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Overall Survival (OS)

Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method. (NCT00602836)
Timeframe: time from registration to death (up to 5 years)

Interventionmonths (Median)
PCR-LenalidomideNA

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Number of Participants With a Response (CR, nPR, PR)

Response criteria described in above outcomes. (NCT00602836)
Timeframe: During treatment (up to 5 years)

InterventionParticipants (Count of Participants)
PCR-Lenalidomide38

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Number of Participants With Complete Response (CR)

"A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months:~- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy" (NCT00602836)
Timeframe: 12 months

Interventionparticipants (Number)
PCR-Lenalidomide14

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Complete Response Rate

"A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. In addition, a bone marrow biopsy with evidence of <30% lymphocytes and no nodules.~Here we report the rate of complete response as the number of patients attaining a CR status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution." (NCT00669318)
Timeframe: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Interventionpercentage of participants (Number)
Treatment (Pentostatin, Alemtuzumab, Rituximab)10

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Overall Response Rate (Complete and Partial Response)

"A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. A bone marrow biopsy with evidence of <30% lymphocytes and no nodules.~Patients who fulfill all criteria for a CR but have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity will be classified as CR with incomplete marrow recovery (CRi).~A Partial Response (PR) requires a 50% reduction in nodes and liver/spleen measurements and at least two of the following: absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, or a >50% reduction in lymphocytes.~Here we report the rate of overall response as the number of patients attaining a CR, PR, or CRi status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution." (NCT00669318)
Timeframe: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Interventionpercentage of patients (Number)
Treatment (Pentostatin, Alemtuzumab, Rituximab)56

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Overall Survival

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT00669318)
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registration

Interventionmonths (Median)
Treatment (Pentostatin, Alemtuzumab, Rituximab)34.1

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Progression-free Survival

The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT00669318)
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registration

Interventionmonths (Median)
Treatment (Pentostatin, Alemtuzumab, Rituximab)7.2

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Time to Retreatment

Time to subsequent therapy is defined to be the time from the registration to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier (NCT00669318)
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registration

Interventionmonths (Median)
Treatment (Pentostatin, Alemtuzumab, Rituximab)9.1

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Actuarial Probability of Donor Hematopoietic Engraftment (Defined as at Least 50% Donor DNA in Bone Marrow at Day 100).

The number of participants with donor hematopoietic engraftment at day 100 is reported in the data table, and the actuarial probability is calculated using the Kaplan-Meier product-limit estimate statistic, as reported in the statistical analysis section below. (NCT00698685)
Timeframe: Day 100 after transplant.

Interventionparticipants (Number)
Preparative Regimen of Pentostatin and Alemtuzumab4

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Non-relapse Mortality at or Before Day 100

The primary safety outcome is indicated by the number of participants who died at or before Day 100 after transplant for any reason other than relapse of disease (Leukemia, Lymphoma, Hodgkin's disease, Hematologic Neoplasms, Multiple Myeloma, Renal Cell Carcinoma). (NCT00698685)
Timeframe: Day 100 after transplant

InterventionParticipants (Number)
Preparative Regimen of Pentostatin and Alemtuzumab3

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Overall Survival

The Kaplan-Meier method will be used to estimate overall survival distributions Overall survival is measured as the time from registration to the time of death due to any cause. (NCT00816595)
Timeframe: Assessed up to 5 years from registration

Interventionmonths (Median)
Arm A: Pentostatin, Cyclophosphamide, Rituximab, and AvastinNA
Arm B: Pentostatin, Cyclophosphamide, and RituximabNA

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Progression-free Survival

The Kaplan-Meier method will be used to estimate progression-free survival distribution. Progression-free survival is defined as the time from registration to the time of progression or death, whichever occurs first. (NCT00816595)
Timeframe: Assessed up to 5 years from registration

Interventionmonths (Median)
Arm A: Pentostatin, Cyclophosphamide, Rituximab, and AvastinNA
Arm B: Pentostatin, Cyclophosphamide, and Rituximab34.1

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Complete and Overall Response Rate

"A Complete Response (CR) requires all of the following for 2 months:~Absence of lymphadenopathy by physical examination (PE)~No hepato- or splenomegaly by PE~Neutrophils >1500/ul, Platelets >100,000/ul. Hemoglobin >11.0 gm/dl, Peripheral blood lymphocytes <4000/uL~Nodular Partial Response (nPR) is defined as a patient qualified for a CR, but regenerative nodules are histologically present on bone marrow samples.~A Clinical Complete Response (CCR) is defined as a patient qualified for a CR, but bone marrow samples are not available.~A Partial Response (PR) requires 50% reduction in 2 of the following: peripheral blood lymphocytes, or the sum of the products of the maximal perpendicular diameters, or the size of liver and/or spleen; and a 50% increase in neutrophils, platelets, or hemoglobin.~Overall response rate is calculated as the number of patients receiving CR, CCR, nPR, or PR as their objective status divided by the total number of evaluable patients." (NCT00816595)
Timeframe: Evaluated after 6 cycles (up to 196 days)

,
Interventionpercentage of patients (Number)
Complete Response (CR) RateOverall Response Rate
Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin50.093.8
Arm B: Pentostatin, Cyclophosphamide, and Rituximab33.396.7

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Count of Patients With Chronic Graft Versus Host Disease (GVHD)

Chronic GVHD was assessed by the 2005 Chronic GVHD Consensus Project. Chronic GVHS may include dryness of the mouth and eyes, weight loss, liver damage and lung damage leading to cough and shortness of breath (i.e. skin Grading: no symptoms = 0, <18% body surface area (BSA) = 1, 19-50% BSA = 2, and >50% BSA = 3); oral cavity Grading: no symptoms = 0, mild symptoms = 1, moderate symptoms =2 and severe symptoms =3)). (NCT00923845)
Timeframe: For the duration of post-transplant follow-up

InterventionParticipants (Count of Participants)
Recipient1

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Count of Patients With Grade II or Greater Acute Graft Versus Host Disease (GVHD) in First 100 Days Post-Transplant

Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD may include rash, diarrhea, and liver damage (i.e. rash Grading: <25% body surface area (BSA) = 1, rash 25-50% BSA = 2, generalized erythroderma = 3, and desquamation and bullae = 4); liver Grading: total bilirubin 2-3 mg/dl = 1, total bilirubin 3-6 mg/dl =2, total bilirubin 6-15 mg/dl =3, and total bilirubin >15 mg/dl = 4)). (NCT00923845)
Timeframe: 100 days post transplant

InterventionParticipants (Count of Participants)
Recipient0

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Count of Patients With Late Acute Graft Versus Host Disease (GVHD) After Day 100 Post-Transplant

Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD may include rash, diarrhea, and liver damage (i.e. rash Grading: <25% body surface area (BSA) = 1, rash 25-50% BSA = 2, generalized erythroderma = 3, and desquamation and bullae = 4); liver Grading: total bilirubin 2-3 mg/dl = 1, total bilirubin 3-6 mg/dl =2, total bilirubin 6-15 mg/dl =3, and total bilirubin >15 mg/dl = 4)). (NCT00923845)
Timeframe: 100 days post-transplant through 5 years post-transplant

InterventionParticipants (Count of Participants)
Recipient4

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Immune Depletion in Cluster of Differentiation 4 (CD4) Cells

Reduction in cluster of differentiation 4 (CD4)+ T cells [change in median values and (range of values)]. (NCT00923845)
Timeframe: Baseline and day 21 (completion of the pentostatin/cyclophosphamide regimen)

InterventionCells/µL (Median)
BaselineDay 21
Recipient50354

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Clinical Regression of Metastatic Renal Cell Carcinoma (Partial Response (PR)) or Complete Remission of Tumor (Complete Response (CR))

Response was assessed by computed tomography measurements and the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest LD recorded since the treatment started or the appearance of one or more new lesions. (NCT00923845)
Timeframe: 6 Months Post-Transplant (Day +100)

Interventionparticipants (Number)
Partial Response (PR)Complete Response (CR)Progressive Disease (PD)Stable Disease (SD)Not Applicable (NA)
Recipient00811

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Count of Patients Having an Infectious Complication Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen

Occurrence of infection by Common Terminology Criteria for Adverse Events (CTCAE). (NCT00923845)
Timeframe: During the 21-day PC regimen

InterventionParticipants (Count of Participants)
Recipient0

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Cluster of Differentiation 8 (CD8)+ T Cells Immune Reconstitution

CD8+ T Cells immune reconstitution is defined as distribution of CD8+ T cells subsets within naïve, central memory, effector memory, and effector memory-RA cells analyzed by flow cytometry. (NCT00923845)
Timeframe: Days 14, 60, and 100 post transplant

InterventionPercent of total CD8 cell subsets (Median)
Day 14Day 60Day 100
Recipient654

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Engraftment Donor T Cell and Myeloid Cell Chimerism

Donor Genetic Elements by variable number tandem repeat-polymerase chain reaction (VNTR-PCR) Analysis. (NCT00923845)
Timeframe: Days 14, 28, 45, and 60 post transplant

InterventionPercent Donor by VNTR-PCR Analysis (Median)
Day 14 donor T cell chimerismDay 28 donor T cell chimerismDay 45 donor T cell chimerismDay 60 donor T cell chimerismDay 14 myeloid cell chimerismDay 28 myeloid cell chimerismDay 45 myeloid cell chimerismDay 60 myeloid cell chimerism
Recipient617274770131826

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Immune Depletion in Cluster of Differentiation 8 (CD8)+ T Cells

Reduction in cluster of differentiation 8 (CD8)+ T cells [change in median values and (range of values)]. (NCT00923845)
Timeframe: Baseline and day 21 (completion of the pentostatin/cyclophosphamide regimen)

Interventioncells/µL (Median)
BaselineDay 21
Recipient23945

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Immune Suppression

Immune suppression is defined by the frequency of elimination of a pre-transplant T cell cytokine value. (NCT00923845)
Timeframe: Cytokine analysis at baseline and within 24 hours of completion of the pentostatin/cyclophosphamide regimen

Intervention% of undetectable cytokine measurements (Number)
Positive at baselineNegative at baselinePositive 24 hours after regimenNegative 24 hours after regimen
Recipient10000100

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Cluster of Differentiation 4 (CD4) T Cells Immune Reconstitution

CD4 T Cells immune reconstitution is defined as distribution of CD4+ T cells subsets within naïve, central memory, effector memory, and effector memory-RA cells analyzed by flow cytometry. (NCT00923845)
Timeframe: Days 14, 60, and 100 post transplant

InterventionPercentage of total CD4 cell subsets (Median)
Day 14Day 60Day 100
Recipient222019

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Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th1 Transcription Factor T-bet

CD4+ T cells were analyzed by flow cytometry for intracellular detection of Tbet transcription factor. (NCT00923845)
Timeframe: Days 14, 60, and 100 post transplant

InterventionPercentage of total CD4+T cells (Median)
Day 14Day 60Day 100
Recipient886

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Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th2 Transcription Factor GATA Binding Protein 3 (GATA-3)

Intra-cellular flow cytometry detection of GATA3 transcription factor. (NCT00923845)
Timeframe: Days 14, 60 and 100 post transplant

InterventionPercentage of total CD4+ T cells (Median)
Day 14Day 60Day 100
Recipient423743

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Count of Participants With Adverse Events

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. (NCT00923845)
Timeframe: 50 months and 6 days

InterventionParticipants (Count of Participants)
Donor0
Recipient12

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Count of Patients Having Neutropenia Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen

Absolute neutrophil count determination by complete blood count methodology (Absolute Neutrophil Count (ANC) < 500 Cells/µL). (NCT00923845)
Timeframe: During the 21-day PC regimen

InterventionParticipants (Count of Participants)
Recipient0

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Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the T-reg Transcription Factor Forkhead Box P3 (FoxP3))

CD4+ T cells were analyzed by flow cytometry for intracellular expression of FoxP3. (NCT00923845)
Timeframe: Days 14, 60, and 100 post transplant

InterventionPercentage of total CD4+ T cells (Median)
Day 14Day 60Day 100
Recipient863

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Overall Response Rate

"The overall response rate will be estimated by the total number of complete or partial responses (CCR, CR, CRi, nPR, or PR) divided by the total number of evaluable patients. Responses will be evaluated using NCI Working Group criteria. Minimum requirements for a Partial Response (PR) requires:~50% decrease in peripheral blood lymphocyte count from the baseline~50% reduction in the sum of the products of the largest measured node or nodal masses on physical examination.~50% reduction in size of liver and/or spleen~50% improvement in neutrophils, platelets and hemoglobin" (NCT01024010)
Timeframe: 14 months

Interventionpercentage of participants (Number)
Arm A: PCO96
Arm B: PCO +O97

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Arm A: Percentage of Complete Responses

"In Arm A: PCO, the primary endpoint of this trial is the percentage of complete responses. The NCI Working Group criteria was used to assess response to therapy:~A Complete Response (CR) is briefly defines as the absence of lymphadenopathy, no heptomegaly nor splenomegaly, neutrophils greater than 1500/ul, platelets > 100,000/ul, hemoglobin >11.0 gm/dl, and peripheral blood lymphocytes <4000uL." (NCT01024010)
Timeframe: 7 months

Interventionpercentage of participants (Number)
Arm A: PCO46

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Arm B: Treatment-free Survival at 18 Months

The primary endpoint Arm B: PCO+O is treatment-free survival rate at 18 months. An event for treatment-free survival will be defined as initiation of subsequent therapy for CLL or death due to any cause. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for event-free survival at 18 months. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. (NCT01024010)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Arm A: PCO87.5
Arm B: PCO +O94.1

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Depth of Response After Ofatumumab Consolidation

The proportion of patients with an improvement in depth of response with the addition of ofatumumab consolidation after PCO induction will be estimated by the number of patients with improvement in response from the time of response evaluation at the completion of PCO to the time of response evaluation at the completion of ofatumumab consolidation divided by the total number of evaluable patients. The hierarchy for depth of response will be in the following increasing order: SD, PR, nPR, CR/CRi with MRD+, CR/CRi with MRD-. An improvement in depth of response will be defined as an improvement of at least one level in the hierarchy. Exact binomial 95% confidence intervals for the true overall improvement rate will be calculated. (NCT01024010)
Timeframe: 14 months

Interventionpercentage of participants (Number)
Arm B: PCO +O25

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Treatment-free Survival

Treatment-free survial is defined as the time from registration to the date of initiation of subsequent treatment for CLL or death due to any cause. The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier. (NCT01024010)
Timeframe: up to 5 years from registration

Interventionmonths (Median)
Arm A: PCO56.6
Arm B: PCO +ONA

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Progression-free Survival

Defined as the time interval from the start of treatment to documented evidence of disease progression. Progressive disease is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum on study LD (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression). (NCT01362790)
Timeframe: 36 months

InterventionMonths (Median)
Meothelioma Pilot Phase Phase Regimen A11.8
Meothelioma Pilot Phase Regimen B8.8
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase8.9
Phase 2 Pleural Mesothelioma Pilot Expansion Phase3.9
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A4.4

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Count of Participants SS1P Cycles Received Following Onstudy

Here are the number of participants who had SS1P cycles during cycle 1-6. (NCT01362790)
Timeframe: Cycles 1-6, up to 180 days

,,,,,
InterventionParticipants (Count of Participants)
SS1P 1 CycleSS1P 2 CyclesSS1P 3 CyclesSS1P 4 CyclesSS1P 5 CyclesSS1P 6 Cycles
Mesothelioma Pilot Phase Regimen A180101
Mesothelioma Pilot Phase Regimen B303110
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A000000
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A211000
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase040300
Phase 2 Pleural Mesothelioma Pilot Expansion Phase581010

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Response Assessment

Response was assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is complete disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease (PD) disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. (NCT01362790)
Timeframe: 52 months and 4 days

,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Mesothelioma Pilot Phase Regimen0061
Mesothelioma Pilot Phase Regimen A0253
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0012
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase0061
Phase 2 Pleural Mesothelioma Pilot Expansion Phase0063

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Duration of Response

DOR is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria and is measured from the time measurement criteria is met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10mm. partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study LD (this includes the baseline sum if that is the smallest on study). (NCT01362790)
Timeframe: up to 2.5 years

InterventionMonths (Median)
Mesothelioma Pilot Phase Regimen A16.3

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Count of Participants With SS1P Antibody Formation

Development of antibodies following treatment with SS1P. The goal was to delay development of antibodies to SS1P so a patient could get a second cycle of therapy with SS1P. (NCT01362790)
Timeframe: On last day of last dosing cycle, end of cycle 1 (day 30)

InterventionParticipants (Count of Participants)
Mesothelioma Pilot Phase Regimen A6
Mesothelioma Pilot Phase Regimen B2
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase3
Phase 2 Pleural Mesothelioma Pilot Expansion Phase7
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A0
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0

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Overall Survival

The Kaplan-Meier was used to determine the probability of overall survival from on-study date until death or last follow-up (calculated from the date of study entry until the date of analysis). (NCT01362790)
Timeframe: 36 months

InterventionMonths (Median)
Mesothelioma Pilot Phase Regimen A8.9
Mesothelioma Pilot Phase Regimen B11.2
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase29.3
Phase 2 Pleural Mesothelioma Pilot Expansion Phase4.2
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A9.3

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Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered SS1P and Pentostatin or Cyclophosphamide

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01362790)
Timeframe: Date treatment consent signed to date off study, approximately 64 months and 26 days

InterventionParticipants (Count of Participants)
Mesothelioma Pilot Phase Regimen A11
Mesothelioma Pilot Phase Regimen B8
Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase7
Phase 2 Pleural Mesothelioma Pilot Expansion Phase15
Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A4
Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A0

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Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"Vz/F was defined as the apparent oral dose volume of distribution of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

InterventionLiters (Geometric Mean)
Day 1Day 15
Ruxolitinib54.050.9

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Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"tmax was defined as the time to reach the maximum plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

Interventionhours (Median)
Day 1Day 15
Ruxolitinib0.8331.00

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Cumulative Incidence of Malignancy Relapse/Recurrence (MR)

Defined as the cumulative incidence rate from competing risk analysis of MR from the date of randomization to hematologic malignancy relapse/recurrence. (NCT03112603)
Timeframe: Months 3, 6, 12, 18, 24, 30, and 36

,
Interventionpercentage of participants (Number)
0 to < 3 months3 to < 6 months6 to < 12 months12 to < 18 months18 to < 24 months24 to <30 months30 to <36 months
Best Available Therapy1.312.656.086.086.086.787.50
Ruxolitinib1.923.225.187.828.488.488.48

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t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"t1/2 was defined as the apparent terminal phase disposition half-life of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

Interventionhours (Geometric Mean)
Day 1Day 15
Ruxolitinib2.402.32

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Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose

All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants with a ≥ 50% reduction in daily corticosteroid dose. (NCT03112603)
Timeframe: from Day 15 up to Day 182

,
Interventionpercentage of participants (Number)
Day 15 to ≤ Day 28Day 29 to ≤ Day 42Day 43 to ≤ Day 56Day 57 to ≤ Day 70Day 71 to ≤ Day 84Day 85 to ≤ Day 98Day 99 to ≤ Day 112Day 113 to ≤ Day 126Day 127 to ≤ Day 140Day 141 to ≤ Day 154Day 155 to ≤ Day 168Day 169 to ≤ Day 182
Best Available Therapy13.233.141.147.951.454.060.466.268.368.371.688.8
Ruxolitinib12.735.048.458.762.369.571.273.272.870.074.681.9

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Percentage of Participants Successfully Tapered Off of All Corticosteroids

All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants who successfully tapered off of all corticosteroids. Participants who completely tapered off corticosteroids refer to those who permanently discontinued steroids as per the dose administration panel and who did not restart steroids in the same interval. Participants who were tapered off and continued follow-up were also counted as being tapered off with 0 dose in subsequent intervals until they discontinued from the main treatment period or restarted steroid treatment. (NCT03112603)
Timeframe: up to Day 179

,
Interventionpercentage of participants (Number)
Day 1 to ≤ Day 28Day 29 to ≤ Day 56Day 57 to ≤ Day 84Day 85 to ≤ Day 112Day 113 to ≤ Day 140Day 141 to ≤ Day 168Day 169 to ≤ Day 179
Best Available Therapy2.65.48.510.312.416.815.9
Ruxolitinib2.59.614.016.319.724.224.1

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Cumulative Incidence of Non-relapse Mortality (NRM)

Defined as the cumulative incidence rate from competing risk analysis for NRM from the date of randomization to the date of death not preceded by underlying disease relapse/recurrence. (NCT03112603)
Timeframe: Months 3, 6, 12, 18, 24, 30, and 36

,
Interventionpercentage of participants (Number)
Month 3Month 6Month 12Month 18Month 24Month 30Month 36
Best Available Therapy4.446.4315.1216.4819.2219.2222.0
Ruxolitinib5.459.1315.3015.9317.8317.8317.83

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Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"Cmax was defined as the maximum observed plasma concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

Interventionnanograms per milliliter (ng/mL) (Geometric Mean)
Day 1Day 15
Ruxolitinib167215

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CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"CL/F was defined as the oral dose clearance of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

InterventionLiters/hour (Geometric Mean)
Day 1Day 15
Ruxolitinib15.615.2

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Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)

"Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The FACT-BMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation participants. The questions were based on a 5-point Likert scale, where 0 corresponds to not at all and 4 corresponds to very much. The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148." (NCT03112603)
Timeframe: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)

,
Interventionscores on a scale (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 5 Day 1Cycle 6 Day 1Cycle 7 Day 1Cycle 9 Day 1Cycle 12 Day 1Cycle 15 Day 1Cycle 18 Day 1Cycle 21 Day 1Cycle 24 Day 1Cycle 27 Day 1Cycle 30 Day 1Cycle 33 Day 1Cycle 36 Day 1Cycle 39 Day 1
Best Available Therapy-0.22-1.82-1.05-0.232.410.851.203.747.588.193.687.845.105.755.674.776.64
Ruxolitinib2.320.621.981.252.914.145.327.265.074.105.245.906.237.535.178.728.65

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Change From Baseline in EQ-5D-5L

The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems. (NCT03112603)
Timeframe: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)

,
Interventionscores on a scale (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 5 Day 1Cycle 6 Day 1Cycle 7 Day 1Cycle 9 Day 1Cycle 12 Day 1Cycle 15 Day 1Cycle 18 Day 1Cycle 21 Day 1Cycle 24 Day 1Cycle 27 Day 1Cycle 30 Day 1Cycle 33 Day 1Cycle 36 Day 1Cycle 39 Day 1
Best Available Therapy-0.01-0.04-0.01-0.030.01-0.00-0.020.020.030.02-0.000.010.030.010.050.040.01
Ruxolitinib0.030.030.040.020.050.070.070.070.070.070.080.070.060.050.000.060.06

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AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"AUClast was defined as the area under the concentration-time curve up to the last measurable concentration of ruxolitinib. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

Interventionng*hour/mL (Geometric Mean)
Day 1Day 15
Ruxolitinib636945

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Best Overall Response (BOR) at Cycle 7 Day 1

BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. This analysis was based on the primary cutoff date (May 2020). (NCT03112603)
Timeframe: up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks)

Interventionpercentage of participants (Number)
Ruxolitinib76.4
Best Available Therapy60.4

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AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses

"AUCinf was defined as the area under the concentration-time curve from time 0 to infinity. Early enrolling participants (approximately the first 8 adult and first 4 adolescent participants) randomized to ruxolitinib arm followed an extensive PK sampling schedule. Subsequent participants randomized to ruxolitinib, any randomized participants receiving ruxolitinib after Cycle 6, and any randomized participants receiving BAT that cross over to ruxolitinib followed the sparse PK sampling schedule." (NCT03112603)
Timeframe: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose

Interventionng*hour/mL (Geometric Mean)
Day 1
Ruxolitinib642

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Utilization of Medical Resources

The percentage of participants with at least one submission to healthcare encounter was assessed. (NCT03112603)
Timeframe: from Baseline to LPLV (approximately 5 years)

Interventionpercentage of participants (Number)
Ruxolitinib57.0
Best Available Therapy65.8

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BOR During Cross-over Treatment With Ruxolitinib

BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. (NCT03112603)
Timeframe: from Crossover Cycle 1 Day 1 to any time point up to and including Crossover Cycle 7 Day 1 (each cycle was comprised of 4 weeks)

Interventionpercentage of participants (Number)
Ruxolitinib Cross-Over Period81.4

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Duration of Response Through Study Completion

DOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1. The analysis included a larger number of participants than the number of participants who achieved CR or PR at Cycle 7 Day 1 (82 ruxolitinib and 42 BAT) because the analysis took into account not only those participants who achieved CR or PR at Cycle 7 Day 1, but also participants who achieved CR or PR before Cycle 7 Day 1 but who may have lost their response at Cycle 7 Day 1. For this reason, the number of participants in this analysis does not align with the best overall response (BOR) at Cycle 7 Day 1. This analysis was based on the cutoff date upon study completion (December 2022). (NCT03112603)
Timeframe: from first response to LPLV (approximately 5 years)

InterventionMonths (Median)
RuxolitinibNA
Best Available Therapy6.4

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Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit

ORR was defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. (NCT03112603)
Timeframe: Cycle 7 Day 1 (each cycle was comprised of 4 weeks)

Interventionpercentage of participants (Number)
Ruxolitinib49.7
Best Available Therapy25.6

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Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occurred after the participant's signed informed consent was obtained. Abnormal laboratory values or test results occurring after informed consent constituted adverse events only if they induced clinical signs or symptoms, were considered clinically significant, required therapy (e.g., hematologic abnormality that required transfusion or hematological stem cell support), or required changes in study medication(s). TEAEs were defined as those AEs that started or worsened during the on-treatment period (either randomized or cross-over period). (NCT03112603)
Timeframe: from Baseline to LPLV (approximately 5 years)

InterventionParticipants (Count of Participants)
Ruxolitinib165
Best Available Therapy148
Ruxolitinib Cross-Over Period70

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ORR at the End of Cycle 3

ORR was defined as the percentage of participants in each arm demonstrating a CR or PR based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. (NCT03112603)
Timeframe: Cycle 4 Day 1 (each cycle was comprised of 4 weeks)

Interventionpercentage of participants (Number)
Ruxolitinib54.5
Best Available Therapy31.1

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Overall Survival (OS)

Overall survival was defined as the time from the date of randomization to the date of death due to any cause. (NCT03112603)
Timeframe: from the date of randomization to the date of death due to any cause up to LPLV (approximately 5 years)

Interventionmonths (Median)
RuxolitinibNA
Best Available TherapyNA

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Rate of Failure-free Survival (FFS)

Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD. (NCT03112603)
Timeframe: Baseline to when the last participant reached Cycle 7 Day 1 (each cycle was comprised of 4 weeks)

Interventionmonths (Median)
RuxolitinibNA
Best Available Therapy5.7

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Rate of FFS at Study Completion

Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD. (NCT03112603)
Timeframe: From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years)

Interventionmonths (Median)
Ruxolitinib38.4
Best Available Therapy5.7

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Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score

"To assess improvement of symptoms based on the total symptom score (TSS); a responder was defined as having achieved a clinically relevant reduction from Baseline of the TSS. The scale consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Participants reported their level of symptom bother over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms." (NCT03112603)
Timeframe: Baseline; Cycle 7 Day 1 (each cycle was comprised of 4 weeks)

Interventionpercentage of participants (Number)
Ruxolitinib24.2
Best Available Therapy11.0

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