treosulfan profile

treosulfan: immunosuppressant; RN given refers to (S-(R*,R*))-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	9882105
CHEMBL ID	455186
CHEBI ID	82557
SCHEMBL ID	5399430
MeSH ID	M0069890

Synonym
l-threitol 1,4-dimethanesulfonate
treosulfan
299-75-2
nsc-39069
ovastat (tn)
D07253
treosulfan (inn)
treosulfanum [inn-latin]
l-threitol, 1,4-bismethanesulfonate
1,2,3,4-butanetetrol, 1,4-dimethanesulfonate, (s-(r,r))-
treosulfano [inn-spanish]
nsc 39069
threitol, 1,4-dimethanesulfonate, (2s,3s)-
ccris 2781
treosulphan
hsdb 6963
einecs 206-081-0
(s-(r,r))-1,2,3,4-butanetetrol, 1,4-dimethanesulfonate
l-threitol, 1,4-bis(methanesulfonate)
(2s,3s)-threitol 1,4-bismethanesulfonate
threitol, 1,4-dimethanesulfonate, l-(+)-
ovastat
chebi:82557 ,
threosulphan
CHEMBL455186
C19557
unii-co61er3epi
co61er3epi ,
who 3103
treosulfanum
treosulfano
treosulfan [usan:inn:ban]
treosulfan [iarc]
treosulfan [who-dd]
treosulfan [hsdb]
treosulfan [inn]
kepcondi
treosulfan [mart.]
treograft
grafapex
treosulfan [usan]
l-threitol 1,4-dimethanesulphonate
graftrevo
trecondyv
S6958
CS-3889
l-threitol-1,4-bis-methanesulfonate
SCHEMBL5399430
HY-16503
AKOS030231132
DB11678
l-threitol 1,4-bis(methanesulfonate)
YCPOZVAOBBQLRI-WDSKDSINSA-N
(2s,3s)-2,3-dihydroxybutane-1,4-diyl dimethanesulfonate
PS-12126
[(2s,3s)-2,3-dihydroxy-4-methylsulfonyloxybutyl] methanesulfonate
(s)-3-boc-amino-1-diazo-3-(4-benzyloxy)phenyl-2-butanone
A912763
treosulphannsc 39069
(2s,3s)-2,3-dihydroxy-4-(methanesulfonyloxy)butyl methanesulfonate
EN300-1703341
rel-(2s,3s)-2,3-dihydroxybutane-1,4-diyl dimethanesulfonate

Class	Description
methanesulfonate ester	An organosulfonic ester resulting from the formal condensation of methanesulfonic acid with the hydroxy group of an alcohol, phenol, heteroarenol, or enol.
[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]

Assay ID	Title	Year	Journal	Article
AID409958	Inhibition of bovine brain MAOA	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID409960	Inhibition of bovine brain MAOB	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	17 (6.32)	18.7374
1990's	19 (7.06)	18.2507
2000's	77 (28.62)	29.6817
2010's	101 (37.55)	24.3611
2020's	55 (20.45)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	67 (23.93%)	5.53%
Reviews	16 (5.71%)	6.00%
Case Studies	21 (7.50%)	4.05%
Observational	5 (1.79%)	0.25%
Other	171 (61.07%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (37)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Allogeneic Hematopoietic Cell Transplantation for Patients With Non-Malignant Disorders Using Treosulfan, Fludarabine, and Thiotepa[NCT03980769]	Phase 2	40 participants (Anticipated)	Interventional	2021-05-05	Recruiting
Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)[NCT02048800]		61 participants (Actual)	Observational	2014-03-31	Completed
Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies[NCT03963024]	Phase 1	9 participants (Actual)	Interventional	2014-02-12	Terminated(stopped due to low rate of enrolment)
A Randomized Phase II Trial Comparing Treosulfan and Melphalan With Melphalan Alone as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Myeloma Patients (TreoMel Trial)[NCT05636787]	Phase 2	120 participants (Anticipated)	Interventional	2023-06-06	Recruiting
Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for the Treatment of Bone Marrow Failure Diseases[NCT04965597]	Phase 2	40 participants (Anticipated)	Interventional	2022-04-19	Recruiting
Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Lymphatic Malignancies[NCT01079013]	Phase 2	40 participants (Anticipated)	Interventional	2010-03-31	Active, not recruiting
A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Antifungal Prophylaxis With Posaconazole.[NCT03434704]	Phase 2	10 participants (Actual)	Interventional	2018-06-18	Completed
Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma[NCT00987636]	Phase 3	907 participants (Actual)	Interventional	2009-10-01	Completed
Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen[NCT00796068]	Phase 2	130 participants (Actual)	Interventional	2009-02-24	Completed
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Acute Myeloid Leukaemia[NCT01063660]	Phase 2	75 participants (Actual)	Interventional	2004-03-31	Completed
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS)[NCT01062490]	Phase 2	45 participants (Actual)	Interventional	2004-11-30	Completed
A Multi-Center Study of Conditioning With Treosulfan, Fludarabine and Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia [NCT00860574]	Phase 2	96 participants (Actual)	Interventional	2009-02-28	Completed
Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard C[NCT00822393]	Phase 3	570 participants (Actual)	Interventional	2008-11-24	Completed
Prospectively Randomized Phase III Study of an Individualized Sensitivity-Directed Combination Chemotherapy Versus DTIC as First-Line Treatment in Stage IV Metastatic Melanoma[NCT00779714]	Phase 3	360 participants (Anticipated)	Interventional	2008-10-31	Recruiting
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies[NCT00598624]	Phase 2	175 participants (Anticipated)	Interventional	2005-09-30	Recruiting
An Open-label, Non-randomized, Prospective Trial to Evaluate the Effect of Renal Function Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics in Patients With AML or MDS Undergoing Allogeneic Hematopoietic Stem Cell Transplantation[NCT05534620]	Phase 1	36 participants (Anticipated)	Interventional	2023-11-30	Not yet recruiting
Randomized Phase II Study to Compare a Combination Therapy With Gemcitabine and Treosulfan Versus a Monotherapy as First-Line Chemotherapy for Patients With Metastatic Ocular Melanoma[NCT00168870]	Phase 2	48 participants (Anticipated)	Interventional	2003-02-28	Recruiting
Third-line Therapy of Multiple Myeloma With Lenalidomide in Combination With Pioglitazone, Dexamethasone and Metronomic Low-dose Chemotherapy With Treosulfan[NCT01010243]	Phase 1/Phase 2	54 participants (Anticipated)	Interventional	2009-10-31	Recruiting
Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia[NCT01949129]	Phase 2/Phase 3	1,000 participants (Anticipated)	Interventional	2013-04-30	Recruiting
A Phase II Study of Treosulfan/Fludarabine/Low Dose Total Body Irradiation as a Preparative Regimen for Children With AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation[NCT01772953]	Phase 2	40 participants (Actual)	Interventional	2013-09-30	Completed
Clinical Phase II Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Paediatric Patients With Non-malignant Diseases[NCT02349906]	Phase 2	106 participants (Actual)	Interventional	2015-04-30	Completed
A Prospective Phase II, Randomized Multi-center Trial of a Combined Modularized Treatment With Metronomic Low-dose Treosulfan, Pioglitazone and Clarithromycin Versus Nivolumab in Patients With Squamous Cell Lung Cancer and Non- Squamous Cell Lung Cancer, [NCT02852083]	Phase 2	86 participants (Anticipated)	Interventional	2016-01-31	Recruiting
Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Patients With Hematological Malignancies Using a Treosulfan-Based Preparative Regimen[NCT04195633]	Phase 2	60 participants (Anticipated)	Interventional	2021-01-25	Recruiting
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia[NCT01423500]	Phase 3	405 participants (Anticipated)	Interventional	2007-01-31	Active, not recruiting
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia[NCT01423747]	Phase 3	400 participants (Anticipated)	Interventional	2003-07-31	Active, not recruiting
Präferenz-Studie Bei älteren Patientinnen Mit Ovarialkarzinomrezidiv: Treosulfan Oral vs. intravenös[NCT00170690]	Phase 3	123 participants (Actual)	Interventional	2004-08-31	Completed
Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study[NCT01063647]	Phase 1/Phase 2	56 participants (Actual)	Interventional	2001-11-30	Completed
Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Chemo-refractory or Previously Untreated Acute Myeloid Leukemia and Myelodysplastic Syndrome.[NCT00491634]	Phase 2	24 participants (Anticipated)	Interventional	2007-06-30	Completed
Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen[NCT00919503]	Phase 2	98 participants (Actual)	Interventional	2009-07-31	Completed
A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia[NCT00253513]	Phase 1/Phase 2	60 participants (Actual)	Interventional	2005-06-30	Completed
Unrelated Reduced Intensity Conditioning With Treosulfan® for Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies[NCT00129155]	Phase 2	30 participants (Anticipated)	Interventional	2005-02-28	Recruiting
A Phase II Randomized Study to Assess Outcomes With Treosulfan-Based Versus Clofarabine-Based Conditioning in Patients With Myelodysplastic Syndromes With Excess Blasts (MDS-EB), or Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Tra[NCT04994808]	Phase 2	80 participants (Anticipated)	Interventional	2023-08-11	Recruiting
Evaluation of Safety and Efficacy of Treosulfan-cytarabine-fludarabine (FLAT) Combination Prior to Autologous Stem Cell Transplant (HSCT) in Elderly Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)[NCT03961919]	Phase 2	15 participants (Actual)	Interventional	2009-02-10	Completed
A Phase II Multicentre, Randomized, Controlled Open-label Study on the Use of Anti-thymocyte Globulin and Rituximab for Immunomodulation of Graft-versus-host Disease in Allogeneic Matched Transplants for Non Malignancies[NCT01810926]	Phase 2	130 participants (Anticipated)	Interventional	2011-09-30	Recruiting
Clinical Open-label Phase 2 Study of Low Dose Treosulfan Based Conditioning Regimen Efficacy in Hematopoietic Stem Cell Transplantation for Children With Nijmegen Breakage Syndrome[NCT04400045]	Phase 2	10 participants (Anticipated)	Interventional	2020-05-22	Recruiting
Clinical Phase II Trial to Describe the Safety and Efficacy of Treosulfan-based Conditioning Therapy Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Paediatric Patients With Haematological Malignancies[NCT02333058]	Phase 2	70 participants (Actual)	Interventional	2014-11-21	Completed
A Randomized Phase II Study of Treosulfan, Fludarabine and Low-Dose TBI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)[NCT01894477]	Phase 2	102 participants (Actual)	Interventional	2013-11-30	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Duration (Days) Until Participants Obtained Platelet Engraftment

Summarized using a range and median of measure in days until participants reached platelet engraftment. Platelet engraftment was defined as the first of 7 consecutive days when the platelet count exceeded 20 x 109/L (untransfused). (NCT00796068)
Timeframe: At 6 months

Intervention	days (Median)
Arm I (Low Risk for Graft Failure)	31
Arm II (High Risk for Graft Failure)	31

Incidence of Acute or Chronic Graft-versus-host Disease (GVHD)

Overall GVHD is determined based on the organ stage, response to treatment and whether GVHD was a major cause of death. Chronic GVHD will be defined according to the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Described as mild, moderate, or severe as graded according to the attached Organ Scoring Sheet. Symptoms consistent with both chronic and acute GVHD occurring after day 100 will be considered overlap chronic GVHD syndrome. (NCT00796068)
Timeframe: At 1 year

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	7
Arm II (High Risk for Graft Failure)	6

Incidence of Clinically Significant Infections

Collected and graded according to the modified National Cancer Institute Common Toxicity Criteria. (NCT00796068)
Timeframe: At 6 months

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	53
Arm II (High Risk for Graft Failure)	61

Incidence of Relapse or Disease Progression

Cumulative incidence estimates using non-relapse mortality as competitive event. (NCT00796068)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	17
Arm II (High Risk for Graft Failure)	11

Non-relapse Mortality

Death of any cause other than relapse or disease progression was considered. (NCT00796068)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	8
Arm II (High Risk for Graft Failure)	10

Number of Participants Surviving by 1 Year

Overall survival was measured from the first day of CBT infusion until death from any cause. (NCT00796068)
Timeframe: At 1 year

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	51
Arm II (High Risk for Graft Failure)	47

Number of Participants Surviving up to 2 Years Without Disease Progression

Progression-free survival is the time interval from start of treatment to documented evidence of disease progression. Disease progression was defined by European LeukemiaNet 2017 criteria and International Working Group (IWG) within 3 years of transplant. (NCT00796068)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	37
Arm II (High Risk for Graft Failure)	41

Number of Participants With Acute Graft-versus-host Disease (GVHD) Grade II-IV by Day 100

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. Diagnosing and grading acute GVHD is based on clinical findings (the organ stage, response to treatment and whether GVHD was a major cause of death) and frequently varies between transplant centers and independent reviewers. (NCT00796068)
Timeframe: Day 100

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	36
Arm II (High Risk for Graft Failure)	37

Number of Participants With Graft Failure/Rejection

"Patients will be considered primary graft failure provided they meet any criteria listed below, in the absence of documented disease persistence/recurrence or active bone marrow infection (ex. Cytomegalovirus (CMV)):~i. Absence of 3 consecutive days with neutrophils >500/u1 combined with host CD3+ peripheral blood chimerism ≥50% at day 42 ii. Absence of 3 consecutive days with neutrophils >500/u1 under any circumstances at day 55 iii. Death after day 28 with neutrophil count <100/u1 without any evidence of engraftment (< 5% donor CD3+) iv. Primary autologous count recovery with < 5% donor CD3+ peripheral blood chimerism at count recovery and without relapse" (NCT00796068)
Timeframe: Up to 100 days

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	2
Arm II (High Risk for Graft Failure)	5

Number of Participants With Secondary Graft Failure

Secondary graft failure is defined as decline of neutrophil count to <500/ul with loss of donor chimerism after day 55 (NCT00796068)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	0
Arm II (High Risk for Graft Failure)	0

Number of Patients With Non-relapse Mortality (NRM)

Defined as death from any cause without sign of disease progression or relapse. Loss to follow up are censored, whereas disease relapse or progression are considered competing risks. (NCT00796068)
Timeframe: At day -200

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	7
Arm II (High Risk for Graft Failure)	6

The Number of Participants Alive at Two-years Follow up.

Overall survival of participants after two-years of follow up. (NCT00796068)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm I (Low Risk for Graft Failure)	50
Arm II (High Risk for Graft Failure)	44

Incidence of Chronic GVHD

(NCT00860574)
Timeframe: at 6 months

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	20

Incidence of Grades II-IV Acute GVHD

(NCT00860574)
Timeframe: at 6 months

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	57

Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood

Donor chimerism was evaluated in peripheral blood T cells (NCT00860574)
Timeframe: Day 28 after HCT

Intervention	percentage of T cells (Median)
Treatment (Allogeneic Transplantation)	100

Non Relapse Mortality (NRM) Incidence

Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression. (NCT00860574)
Timeframe: At 6 months

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	6

Non Relapse Mortality Incidence

(NCT00860574)
Timeframe: 1 year after HCT

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	6

Overall Survival (OS)

(NCT00860574)
Timeframe: at 2 years

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	71

Relapse Incidence

(NCT00860574)
Timeframe: At 6 months

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	18

Relapse-free Survival

(NCT00860574)
Timeframe: at 2 years

Intervention	Participants (Count of Participants)
Treatment (Allogeneic Transplantation)	62

Disease Response at One Year Following Hematopoietic Cell Transplantation

Number of patients with no evidence of disease at one year following transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	78
Regimen B (UBCT)	8

Immune Reconstitution Following Hematopoietic Cell Transplantation

Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	39
Regimen B (UBCT)	4

Non-relapse Mortality

Number of patients who experienced non-relapse mortality by 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	2
Regimen B (UBCT)	5

Number of Participants With Infections

Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant (NCT00919503)
Timeframe: 100 days post transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	57
Regimen B (UBCT)	9

Number of Patients With Grade II-IV Acute Graft-versus-host Disease

Number of patients diagnosed with overall grade II-IV acute GVHD by Day 100 post transplant (NCT00919503)
Timeframe: Day 100 post transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	44
Regimen B (UBCT)	8

Number of Patients With of Chronic Graft-versus-host Disease

Number of patients diagnosed with chronic GVHD and requiring systemic immunosuppression within 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	29
Regimen B (UBCT)	5

Overall Survival

Number of patients alive at 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	80
Regimen B (UBCT)	9

Preliminary Efficacy

Number of patients engrafted (>5% donor CD3+ peripheral blood chimerisms) at 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

Intervention	Participants (Count of Participants)
Regimen A (PBSCT and BMT)	83
Regimen B (UBCT)	10

Donor Chimerism CD3 at 100 Days Post Transplant

Number of patients with peripheral blood donor chimerism for CD3 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. (NCT00919503)
Timeframe: Day 100 post transplant

Intervention	Participants (Count of Participants)
	Greater than equal to 95%	50 - 94%	5-49%	Less than 5%
Regimen A (PBSCT and BMT)	49	29	6	0
Regimen B (UBCT)	7	2	1	1

Donor Chimerism CD33 at Day 100 Post Transplant

Number of patients with peripheral blood donor chimerism for CD33 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. (NCT00919503)
Timeframe: 100 days post transplant

Intervention	Participants (Count of Participants)
	Greater than equal to 95%	50-94%	5-49%	Less than 5%
Regimen A (PBSCT and BMT)	72	8	4	0
Regimen B (UBCT)	7	2	2	1

Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)

NRM (Non relapse mortality) - death not attributed to the primary cancer. (NCT00253513)
Timeframe: 200 days

Intervention	percent of participants (Number)
Treosulfan and Fludarabine Conditioning	5

Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.

(NCT00253513)
Timeframe: One year

Intervention	participants (Number)
Treosulfan and Fludarabine Conditioning	58

Number of Patients Experiencing Graft Failure

Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither. (NCT00253513)
Timeframe: 42 days

Intervention	participants (Number)
	acute graft vs. host disease (aGVHD)	chronic graft vs. host disease (cGVHD)
Treosulfan and Fludarabine Conditioning	36	31

Number of Patients Experiencing Regimen-related Toxicity Events in Study Population

Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal (NCT00253513)
Timeframe: 34 days and 2 years

Intervention	participants (Number)
	Severe Regimen Related Toxicity (RRT)	Nonrelapse mortality at 2 years
Treosulfan and Fludarabine Conditioning	2	5

Number of Participants That Did Not Progress Within 6 Months

Progression is defined as relapse (NCT01894477)
Timeframe: At 6 months post-transplant

Intervention	Participants (Count of Participants)
Arm A (Treosulfan, Fludarabine Phosphate)	20
Arm B (Treosulfan, Fludarabine Phosphate, TBI)	48

Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

(NCT01894477)
Timeframe: Up to 84 days

Intervention	Participants (Count of Participants)
Arm A (Treosulfan, Fludarabine Phosphate)	29
Arm B (Treosulfan, Fludarabine Phosphate, TBI)	50

Article	Year
Metformin pretreatment ameliorates busulfan-induced liver endothelial toxicity during haematopoietic stem cell transplantation. PloS one, Volume: 18, Issue: 10	2023
Hematopoietic stem cell transplantation with reduced toxicity conditioning regimen in mitochondrial neurogastrointestinal encephalopathy syndrome. Pediatric blood & cancer, Volume: 70, Issue: 7	2023
Risk factors for mixed chimerism in children with hemophagocytic lymphohistiocytosis after reduced toxicity conditioning. Pediatric blood & cancer, Volume: 67, Issue: 9	2020
Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens. Pediatric hematology and oncology, Volume: 37, Issue: 5	2020
Skin toxicity following treosulfan-thiotepa-fludarabine-based conditioning regimen in non-malignant pediatric patients undergoing hematopoietic stem cell transplantation. Pediatric transplantation, Volume: 24, Issue: 1	2020
Treosulfan-based reduced toxicity hematopoietic stem cell transplantation in X-linked agammaglobulinemia: A cost-effective alternative to long-term immunoglobulin replacement in developing countries. Pediatric transplantation, Volume: 24, Issue: 1	2020
Feasibility and Safety of Treosulfan, Melphalan, and Thiotepa-Based Megachemotherapy with Autologous or Allogeneic Stem Cell Transplantation in Heavily Pretreated Children with Relapsed or Refractory Neuroblastoma. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume: 25, Issue: 9	2019
Outcome of treosulfan-based reduced-toxicity conditioning regimens for HSCT in high-risk patients with primary immune deficiencies. Pediatric transplantation, Volume: 22, Issue: 7	2018
Treosulfan based reduced toxicity conditioning followed by allogeneic stem cell transplantation in patients with myelofibrosis. Hematological oncology, Volume: 34, Issue: 3	2016
A phase II study to determine the efficacy and safety of oral treosulfan in patients with advanced pre-treated Ewing sarcoma ISRCTN11631773. Pediatric blood & cancer, Volume: 62, Issue: 1	2015
Cytostatic conditioning in experimental allogeneic bone marrow transplantation: Busulfan causes less early gastrointestinal toxicity but Treosulfan results in improved immune reconstitution. Immunopharmacology and immunotoxicology, Volume: 36, Issue: 2	2014
Escalating topotecan in combination with treosulfan has acceptable toxicity in advanced pediatric sarcomas. Pediatric hematology and oncology, Volume: 30, Issue: 4	2013
Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood, Jul-12, Volume: 120, Issue: 2	2012
A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis. Journal of cancer research and clinical oncology, Volume: 138, Issue: 8	2012
Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity. Bone marrow transplantation, Volume: 47, Issue: 10	2012
Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica, Volume: 96, Issue: 9	2011
Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia. British journal of haematology, Volume: 142, Issue: 2	2008
Cytotoxic effects of treosulfan and busulfan against leukemic cells of pediatric patients. Cancer chemotherapy and pharmacology, Volume: 62, Issue: 5	2008
Cytotoxicity of treosulfan and busulfan on pediatric tumor cell lines. Anti-cancer drugs, Volume: 17, Issue: 6	2006
Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation. Blood, Jan-15, Volume: 103, Issue: 2	2004
CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in malignant glioma cells in vitro and in vivo. International journal of oncology, Volume: 21, Issue: 1	2002
[Treosulfan displays cytotoxic effect on spheroids of primary cell cultures of renal cell carcinoma independent of p-glycoprotein expression]. Der Urologe. Ausg. A, Volume: 37, Issue: 4	1998
Potentiation of treosulfan toxicity by the glutathione-depleting agent buthionine sulfoximine in human malignant glioma cells: the role of bcl-2. Biochemical pharmacology, Feb-01, Volume: 55, Issue: 3	1998
Airborne cytotoxicity in the DiSC assay caused by solutions of treosulfan but not busulphan. Cytotechnology, Volume: 16, Issue: 2	1994
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Evaluation of treosulfan cumulative exposure in paediatric patients through population pharmacokinetics and dosing simulations. British journal of clinical pharmacology, Volume: 89, Issue: 4	2023
Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. British journal of clinical pharmacology, Volume: 88, Issue: 4	2022
Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model. Pharmacological reports : PR, Volume: 72, Issue: 5	2020
Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation. British journal of clinical pharmacology, Volume: 85, Issue: 9	2019
Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives. Clinical pharmacokinetics, Volume: 57, Issue: 10	2018
Clinical bioanalysis of treosulfan and its epoxides: The importance of collected blood processing for valid pharmacokinetic results. Journal of pharmaceutical and biomedical analysis, May-10, Volume: 153	2018
Formation Rate-Limited Pharmacokinetics of Biologically Active Epoxy Transformers of Prodrug Treosulfan. Journal of pharmaceutical sciences, Volume: 105, Issue: 5	2016
Development and Validation of a High Pressure Liquid Chromatography-UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studies. Journal of chromatographic science, Volume: 54, Issue: 3	2016
Pharmacokinetics of treosulfan and its active monoepoxide in pediatric patients after intravenous infusion of high-dose treosulfan prior to HSCT. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Feb-20, Volume: 68	2015
Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics. Drug discovery today, Volume: 19, Issue: 10	2014
Pharmacokinetics of treosulfan in pediatric patients undergoing hematopoietic stem cell transplantation. Therapeutic drug monitoring, Volume: 36, Issue: 4	2014
Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT. Bone marrow transplantation, Volume: 42 Suppl 2	2008
Determination of treosulfan in plasma and urine by HPLC with refractometric detection; pharmacokinetic studies in children undergoing myeloablative treatment prior to haematopoietic stem cell transplantation. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, May-01, Volume: 850, Issue: 1-2	2007
Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research, Volume: 6, Issue: 11	2000
Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer. Cancer chemotherapy and pharmacology, Volume: 45, Issue: 6	2000
Clinical pharmacokinetics of intravenous treosulfan in patients with advanced solid tumors. Cancer chemotherapy and pharmacology, Volume: 42, Issue: 2	1998
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Determination of Treosulfan and Fludarabine in Plasma by Turbulent Flow Liquid Chromatography-Tandem Mass Spectrometry (TFLC-MS/MS). Methods in molecular biology (Clifton, N.J.), Volume: 2737	2024
Evaluation of treosulfan cumulative exposure in paediatric patients through population pharmacokinetics and dosing simulations. British journal of clinical pharmacology, Volume: 89, Issue: 4	2023
Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. British journal of clinical pharmacology, Volume: 88, Issue: 4	2022
Modelling of neutrophil dynamics in children receiving busulfan or treosulfan for haematopoietic stem cell transplant conditioning. British journal of clinical pharmacology, Volume: 86, Issue: 8	2020
Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation. British journal of clinical pharmacology, Volume: 85, Issue: 9	2019
Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume: 24, Issue: 8	2018
Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives. Clinical pharmacokinetics, Volume: 57, Issue: 10	2018
Clinical bioanalysis of treosulfan and its epoxides: The importance of collected blood processing for valid pharmacokinetic results. Journal of pharmaceutical and biomedical analysis, May-10, Volume: 153	2018
Transport of treosulfan and temozolomide across an in-vitro blood-brain barrier model. Anti-cancer drugs, Volume: 26, Issue: 7	2015
Pharmacokinetics of treosulfan in pediatric patients undergoing hematopoietic stem cell transplantation. Therapeutic drug monitoring, Volume: 36, Issue: 4	2014
Intermediate intensity conditioning regimen containing FLAMSA, treosulfan, cyclophosphamide, and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia. Annals of hematology, Volume: 91, Issue: 1	2012
Diffusion-weighted imaging as predictor of therapy response in an animal model of Ewing sarcoma. Investigative radiology, Volume: 44, Issue: 5	2009
Preclinical studies of treosulfan demonstrate potent activity in Ewing's sarcoma. Cancer chemotherapy and pharmacology, Volume: 62, Issue: 1	2008
Cytotoxicity of treosulfan and busulfan on pediatric tumor cell lines. Anti-cancer drugs, Volume: 17, Issue: 6	2006
Clinical evaluation of in vitro chemosensitivity testing: the example of uveal melanoma. Journal of cancer research and clinical oncology, Volume: 130, Issue: 7	2004
Antileukaemic activity of treosulfan in xenografted human acute lymphoblastic leukaemias (ALL). European journal of cancer (Oxford, England : 1990), Volume: 39, Issue: 6	2003
Individualized long-term chemotherapy for recurrent ovarian cancer after failing high-dose treatment. Anti-cancer drugs, Volume: 13, Issue: 2	2002
Acute non-lymphocytic leukemia in patients with ovarian carcinoma following long-term treatment with Treosulfan (= dihydroxybusulfan). Cancer, Jan-01, Volume: 45, Issue: 1	1980
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach. British journal of clinical pharmacology, Volume: 88, Issue: 4	2022
Treosulfan in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation. Drugs of today (Barcelona, Spain : 1998), Volume: 56, Issue: 6	2020
In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia. Cancer chemotherapy and pharmacology, Volume: 74, Issue: 2	2014
Escalating topotecan in combination with treosulfan has acceptable toxicity in advanced pediatric sarcomas. Pediatric hematology and oncology, Volume: 30, Issue: 4	2013
Preclinical analysis of treosulfan in combination with total body irradiation as conditioning regimen prior to bone marrow transplantation in rats. Immunopharmacology and immunotoxicology, Volume: 31, Issue: 4	2009
Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications. Bone marrow transplantation, Volume: 35, Issue: 3	2005
The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours. BMC cancer, Nov-23, Volume: 4	2004
Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study. Cancer chemotherapy and pharmacology, Volume: 52, Issue: 5	2003
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

treosulfan

Description

Cross-References

Synonyms (62)

Drug Classes (1)

Bioassays (2)

Research

Studies (269)

Study Types

Clinical Trials (37)

Trial Overview

Trial Outcomes

Duration (Days) Until Participants Obtained Platelet Engraftment

Incidence of Acute or Chronic Graft-versus-host Disease (GVHD)

Incidence of Clinically Significant Infections

Incidence of Relapse or Disease Progression

Non-relapse Mortality

Number of Participants Surviving by 1 Year

Number of Participants Surviving up to 2 Years Without Disease Progression

Number of Participants With Acute Graft-versus-host Disease (GVHD) Grade II-IV by Day 100

Number of Participants With Graft Failure/Rejection

Number of Participants With Secondary Graft Failure

Number of Patients With Non-relapse Mortality (NRM)

The Number of Participants Alive at Two-years Follow up.

Incidence of Chronic GVHD

Incidence of Grades II-IV Acute GVHD

Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood

Non Relapse Mortality (NRM) Incidence

Non Relapse Mortality Incidence

Overall Survival (OS)

Relapse Incidence

Relapse-free Survival

Disease Response at One Year Following Hematopoietic Cell Transplantation

Immune Reconstitution Following Hematopoietic Cell Transplantation

Non-relapse Mortality

Number of Participants With Infections

Number of Patients With Grade II-IV Acute Graft-versus-host Disease

Number of Patients With of Chronic Graft-versus-host Disease

Overall Survival

Preliminary Efficacy

Donor Chimerism CD3 at 100 Days Post Transplant

Donor Chimerism CD33 at Day 100 Post Transplant

Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)

Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.

Number of Patients Experiencing Graft Failure

Number of Patients Experiencing Regimen-related Toxicity Events in Study Population

Number of Participants That Did Not Progress Within 6 Months

Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Related Drugs (561)

Related Conditions (968)

Research Highlights

Safety/Toxicity (25)

Pharmacokinetics (16)

Bioavailability (1)

Dosage (18)

Interactions (8)