Compounds > imetelstat
Page last updated: 2024-11-13

imetelstat

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Cross-References

ID SourceID
PubMed CID72941969
MeSH IDM0545573

Synonyms (1)

Synonym
imetelstat

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The most frequent adverse events were fatigue (55%), diarrhea (51%), nausea (44%), and hypertension (42%)."( Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.
Bass, MB; Benjamin, R; Chang, DD; Herbst, RS; Koutsoukos, A; Kurzrock, R; Mulay, M; Ng, C; Polverino, A; Purdom, M; Rosen, LS; Silverman, J; Sun, YN; Van Vugt, A; Wiezorek, JS; Xu, RY, 2007)		0.34
" Sixteen patients (62%) experienced motesanib-related adverse events, most commonly lethargy (n=6), diarrhoea (n=4), fatigue (n=3), headache (n=3), and nausea (n=3)."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008)		0.35
" The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%)."( Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
Bastholt, L; Daumerie, C; Droz, JP; Elisei, R; Eschenberg, MJ; Jarzab, B; Juan, T; Locati, LD; Martins, RG; Pacini, F; Schlumberger, MJ; Sherman, SI; Stepan, DE; Sun, YN; Wirth, LJ, 2009)		0.35
" The most common motesanib treatment-related grade 3 adverse events included hypertension (23%), fatigue (9%), and diarrhea (5%)."( Efficacy and safety of motesanib, an oral inhibitor of VEGF, PDGF, and Kit receptors, in patients with imatinib-resistant gastrointestinal stromal tumors.
Baker, L; Benjamin, RS; Blay, JY; Bui, BN; Duyster, J; Hartmann, JT; McCoy, S; Reichardt, P; Rosen, LS; Schöffski, P; Schuetze, S; Skubitz, K; Stepan, DE; Sun, YN; Van Oosterom, A, 2011)		0.37

Pharmacokinetics

ExcerptReferenceRelevance
" Patients were randomized to receive a single oral dose of ketoconazole 400 mg either on day 8 (Sequence 1; n = 7) or day 15 (Sequence 2; n = 7), while pharmacokinetic samples were collected."( Effect of coadministration of ketoconazole, a strong CYP3A4 inhibitor, on pharmacokinetics and tolerability of motesanib diphosphate (AMG 706) in patients with advanced solid tumors.
Chen, L; Heath, EI; Ingram, M; Lorusso, P; Malburg, L; McGreivy, J; Melara, R; Pilat, MJ; Sun, YN; Wiezorek, J; Yan, L, 2008)		0.35
" In conclusion, treatment with motesanib plus gemcitabine was well tolerated, with adverse event and pharmacokinetic profiles similar to that observed in monotherapy studies."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008)		0.35
" Motesanib concentrations were fitted to a 2-compartment population pharmacokinetic model."( Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.
Bruno, R; Claret, L; Kuchimanchi, M; Lu, JF; Melara, R; Sun, YN; Sutjandra, L, 2010)		0.36

Compound-Compound Interactions

ExcerptReferenceRelevance
"The aim of this open-label phase 1b study was to assess the safety and pharmacokinetics of motesanib in combination with gemcitabine in patients with advanced solid tumours."( Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
Lipton, L; McCoy, S; McGreivy, J; Price, TJ; Rosenthal, MA; Sun, YN, 2008)		0.35
"Treatment with motesanib was tolerable when combined with carboplatin/paclitaxel and/or panitumumab, with little effect on motesanib pharmacokinetics at the 125-mg once daily dose level."( Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer.
Blumenschein, GR; Gladish, G; McGreivy, J; O'Rourke, T; Parson, M; Reckamp, K; Sandler, A; Stephenson, GJ; Sun, YN; Ye, Y, 2010)		0.36
"This phase Ib study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 102, a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in combination with bevacizumab or motesanib in patients with advanced solid tumors."( A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.
Anderson, A; Beaupre, DM; Deng, H; Leitch, IM; Oliner, KS; Park, DJ; Rosen, PJ; Shubhakar, P; Sweeney, CJ; Yee, LK; Zhu, M, 2010)		0.36
"AMG 102 in combination with bevacizumab was well tolerated."( A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.
Anderson, A; Beaupre, DM; Deng, H; Leitch, IM; Oliner, KS; Park, DJ; Rosen, PJ; Shubhakar, P; Sweeney, CJ; Yee, LK; Zhu, M, 2010)		0.36
"This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011)		0.37
"Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6)."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011)		0.37
" The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011)		0.37
" Motesanib 125 mg QD was tolerable only in combination with erlotinib alone."( Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study.
Adewoye, AH; Desai, J; Johnson, J; Kotasek, D; McCoy, S; Price, T; Siu, LL; Sun, YN; Tebbutt, N; Welch, S, 2011)		0.37
" We investigated the antitumor activity of motesanib, a selective antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, platelet-derived growth factor receptor, and Kit, alone and combined with chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI-H1299, and NCI-H1650) containing diverse genetic mutations."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012)		0.38
" When combined with cisplatin, motesanib significantly inhibited the growth of Calu-6, NCI-H358, and NCI-H1650 tumor xenografts compared with either single agent alone (P < 0."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012)		0.38
"These data demonstrate that motesanib had antitumor activity against five different human NSCLC xenograft models containing diverse genetic mutations, and that it had enhanced activity when combined with cisplatin or docetaxel."( Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.
Coxon, A; Kaufman, S; Polverino, A; Saffran, D; Schmidt, J; Starnes, C; Sweet, H; Wang, H; Weishuhn, D; Xu, M; Ziegler, B, 2012)		0.38
" Moreover, imetelstat alone and in combination with trastuzumab reduced the CSC fraction and inhibited CSC functional ability, as shown by decreased mammosphere counts and invasive potential."( The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2+ breast cancer cells.
Herbert, BS; Koziel, JE, 2015)		0.42
"In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29)."( Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.
Altun, A; Ataseven, H; Kaya, TT; Koyluoglu, G; Turgut, NH, 2016)		0.43

Bioavailability

ExcerptReferenceRelevance
" A novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4, platelet-derived growth factor receptor, and Kit receptors in preclinical models."( AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts.
Alva, G; Bready, J; Cattley, R; Chen, D; Coxon, A; DeMelfi, T; Diaz, Z; Estrada, J; Gan, Y; Kaufman, S; Kendall, R; Kumar, G; Meyer, J; Montestruque, S; Neervannan, S; Patel, V; Polverino, A; Radinsky, R; Starnes, C; Talvenheimo, J; Tasker, A; Wang, L, 2006)		0.33
"AMG 706 is an investigational, orally bioavailable inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and stem-cell factor receptor."( Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.
Bass, MB; Benjamin, R; Chang, DD; Herbst, RS; Koutsoukos, A; Kurzrock, R; Mulay, M; Ng, C; Polverino, A; Purdom, M; Rosen, LS; Silverman, J; Sun, YN; Van Vugt, A; Wiezorek, JS; Xu, RY, 2007)		0.34
" Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations."( Motesanib and advanced NSCLC: experiences and expectations.
Blumenschein, GR; Raghav, KP, 2011)		0.37

Dosage Studied

ExcerptRelevanceReference
" The population pharmacokinetic/pharmacodynamic model provides a tool for predicting tumor response to the drug to support the dosing regimen of motesanib in thyroid cancer patients."( Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.
Bruno, R; Claret, L; Kuchimanchi, M; Lu, JF; Melara, R; Sun, YN; Sutjandra, L, 2010)		0.36
" Dose-response simulations were performed in patients with differentiated thyroid cancer."( Development of a modeling framework to simulate efficacy endpoints for motesanib in patients with thyroid cancer.
Bruno, R; Claret, L; Lu, JF; Sun, YN, 2010)		0.36
" On the other hand, the optimal combination and dosage of these drugs, selection of the apropriate biomarker and better understanding of the conflicting role of PDGFR and FGFR signaling in angiogenesis remain future challenges."( [Possibilities for inhibiting tumor-induced angiogenesis: results with multi-target tyrosine kinase inhibitors].
Döme, B; Török, S, 2012)		0.38
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (117)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's20 (17.09)29.6817
2010's82 (70.09)24.3611
2020's15 (12.82)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials33 (28.21%)5.53%
Reviews26 (22.22%)6.00%
Case Studies3 (2.56%)4.05%
Observational0 (0.00%)0.25%
Other55 (47.01%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (31)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor [NCT04576156]Phase 3320 participants (Anticipated)Interventional2021-04-12Recruiting
A Phase II Clinical and Biologic Study of AMG 706 and Octreotide in Patients With Low-Grade Neuroendocrine Tumors [NCT00427349]Phase 246 participants (Actual)Interventional2008-11-07Completed
An Open Label Treatment Extension Study of AMG 706 [NCT00360867]Phase 294 participants (Actual)Interventional2005-12-31Terminated(stopped due to Amgen decision)
A Randomized Phase II Study Of Imetelstat (GRN163L) In Combination With Paclitaxel (With Or Without Bevacizumab) in Patients With Locally Recurrent Or Metastatic Breast Cancer [NCT01256762]Phase 2166 participants (Actual)Interventional2010-11-30Completed
A Randomized Phase II Study of Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy for Advance Non-small Cell Lung Cancer(NSCLC) [NCT01137968]Phase 2116 participants (Actual)Interventional2010-05-31Completed
An Open-label, Dose-finding Study to Evaluate the Safety and Pharmacokinetics (PK) of AMG 706 With Carboplatin/Paclitaxel, AMG 706 With Panitumumab and AMG 706 With Panitumumab and Carboplatin/Paclitaxel in the Treatment of Subjects With Advanced Non-Smal [NCT00094835]Phase 1/Phase 251 participants (Actual)Interventional2005-01-31Completed
A Phase 2, Multicenter, Open Label, Randomized Trial of AMG 706 or Bevacizumab in Combination With Paclitaxel and Carboplatin for Advanced Non-squamous Non-small Cell Lung Cancer [NCT00369070]Phase 2186 participants (Actual)Interventional2007-01-31Terminated
A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer [NCT01265927]Phase 110 participants (Actual)Interventional2011-01-31Completed
Phase I/II Trial of Motesanib in Combination With Ixabepilone and Capecitabine in Women With Locally Recurrent or Metastatic Breast Cancer [NCT01349088]Phase 1/Phase 20 participants (Actual)Interventional2013-12-31Withdrawn
A Phase II Evaluation of AMG 706 (IND # 79,697) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT00574951]Phase 223 participants (Actual)Interventional2007-12-31Terminated(stopped due to Study was stopped for severe toxicity causing concern for patients)
A Randomized, Single-Blind, Multicenter Phase 2 Study to Evaluate the Activity of 2 Dose Levels of Imetelstat in Subjects With Intermediate-2 or High-Risk Myelofibrosis (MF) Relapsed/Refractory to Janus Kinase (JAK) Inhibitor [NCT02426086]Phase 2107 participants (Actual)Interventional2015-08-28Completed
A Phase I Study of GRN163L in Combination With Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT00718601]Phase 140 participants (Anticipated)Interventional2008-07-31Completed
An Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 386 With AMG 706, AMG 386 With Bevacizumab, AMG 386 With Sorafenib, and AMG 386 With Sunitinib in Adult Patients With Advanced Solid Tumors [NCT00861419]Phase 188 participants (Anticipated)Interventional2005-12-31Completed
A Pilot Study of Imetelstat Given Intravenously on Day 1 and 8 of a 21 Day Schedule Alone and With Standard 13-Cis-Retinoic Acid in Children With Recurrent and/or Refractory Neuroblastoma [NCT01916187]Phase 10 participants (Actual)Interventional2013-07-30Withdrawn(stopped due to drug company withdrew support following re-examination of benefit-risk assessment for the investigational use of imetelstat in this population)
A Phase II Study of Imetelstat (GRN163L, NSC# 754228) in Children With Relapsed or Refractory Solid Tumors [NCT02011126]Phase 20 participants (Actual)Interventional2014-06-30Withdrawn(stopped due to IND no longer available.)
A Phase 1 Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of GRN163L in Patients With Refractory or Relapsed Multiple Myeloma [NCT00594126]Phase 120 participants (Actual)Interventional2007-11-30Completed
A Phase I Study of GRN163L in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00510445]Phase 127 participants (Actual)Interventional2007-07-31Completed
A Phase II Trial to Evaluate the Activity of Imetelstat (GRN163L) in Patients With Essential Thrombocythemia or Polycythemia Vera Who Require Cytoreduction and Have Failed or Are Intolerant to Previous Therapy, or Who Refuse Standard Therapy [NCT01243073]Phase 220 participants (Actual)Interventional2010-12-31Completed
A Phase II Trial to Determine the Effect of Imetelstat (GRN163L) on Patients With Previously Treated Multiple Myeloma [NCT01242930]Phase 213 participants (Actual)Interventional2010-11-30Completed
An Open-Label, Randomized, Phase 1b Study Evaluating the Effect of Different Doses of AMG 706 on the Gallbladder in Subjects With Advanced Solid Tumors [NCT00448786]Phase 149 participants (Actual)Interventional2007-02-28Completed
Expanded Access Treatment With Imetelstat For Adult Participants With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Are Transfusion-Dependent And Have Failed to Respond or Have Lost Response or Are Ineligible For Erythropoiesis-S [NCT05937568]0 participants Expanded AccessAvailable
A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies [NCT01731951]Phase 280 participants (Actual)Interventional2012-10-29Completed
A Phase Ib, Open-Label, Sequential, Dose-Finding, Study of AMG 706 in Combination With Gemcitabine to Treat Subjects With Solid Tumors [NCT00324597]Phase 118 participants (Anticipated)Interventional2005-10-31Active, not recruiting
A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and MTD of GRN163L in Patients With Refractory or Relapsed Solid Tumor Malignancies [NCT00310895]Phase 185 participants (Anticipated)Interventional2006-03-31Completed
An Open Label, Phase 1/1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Patients With Myelofibrosis [NCT05371964]Phase 141 participants (Anticipated)Interventional2022-05-04Recruiting
A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination With Paclitaxel, or Open-Label Bevacizumab in Combination With Paclitaxel, as First Line Therapy in Women With HER2 Negative Locally Recurrent or Metastatic Breast Cance [NCT00356681]Phase 2282 participants (Actual)Interventional2006-12-31Terminated(stopped due to Sponsor decision to close study)
A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients With HR Myelodysplastic Syndromes or AML Failing HMA-based Therapy [NCT05583552]Phase 246 participants (Anticipated)Interventional2023-06-05Recruiting
A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas [NCT01568632]Phase 10 participants (Actual)Interventional2012-03-31Withdrawn
A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas [NCT01273090]Phase 134 participants (Actual)Interventional2011-05-31Completed
A Molecular Biology and Phase II Study of Imetelstat (GRN163L) in Children With Recurrent High-Grade Glioma, Ependymoma and Diffuse Intrinsic Pontine Glioma [NCT01836549]Phase 243 participants (Actual)Interventional2013-03-31Terminated(stopped due to Due to several intracranial hemorrhages and recommendation by the PBTC DSMB.)
A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment [NCT02598661]Phase 2/Phase 3289 participants (Actual)Interventional2015-11-24Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00094835 (11) [back to overview]Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
NCT00094835 (11) [back to overview]Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
NCT00094835 (11) [back to overview]Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
NCT00094835 (11) [back to overview]Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
NCT00094835 (11) [back to overview]Percentage of Participants With an Overall Objective Response
NCT00094835 (11) [back to overview]Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
NCT00094835 (11) [back to overview]Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
NCT00094835 (11) [back to overview]Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
NCT00427349 (3) [back to overview]Objective Response Rate
NCT00427349 (3) [back to overview]Overall Survival
NCT00427349 (3) [back to overview]Four-month Progression-free Survival Rate
NCT00574951 (3) [back to overview]Duration of Overall Survival (OS)
NCT00574951 (3) [back to overview]Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
NCT00574951 (3) [back to overview]Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
NCT01731951 (12) [back to overview]Blastic MF/AML Participants: Percentage of Participants With Overall Response
NCT01731951 (12) [back to overview]MDS Participants: Duration of Response Per IWG Criteria
NCT01731951 (12) [back to overview]MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria
NCT01731951 (12) [back to overview]MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria
NCT01731951 (12) [back to overview]MDS Participants: Time to Response
NCT01731951 (12) [back to overview]MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT
NCT01731951 (12) [back to overview]MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria
NCT01731951 (12) [back to overview]MF Participants: Percentage of Participants With Overall Response (OR) - (Clinical Improvement[CI] or Partial Remission[PR] or Complete Remission[CR]) Per International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria
NCT01731951 (12) [back to overview]MF Participants: Time to Response
NCT01731951 (12) [back to overview]Overall Survival (OS)
NCT01731951 (12) [back to overview]Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs and Treatment Related Adverse Events
NCT01731951 (12) [back to overview]Number of Participants With Spleen Response Per IWG-MRT Criteria
NCT01836549 (5) [back to overview]Number of Participants With Telomerase Inhibition
NCT01836549 (5) [back to overview]Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction
NCT01836549 (5) [back to overview]Phase II: Stratum-specific Objective Response (CR+PR) Rate
NCT01836549 (5) [back to overview]Stratum-specific Progression-free Survival (PFS) (Phase II)
NCT01836549 (5) [back to overview]Number of Patients With Telomerase Expression Data by Detection of hTERT mRNA and TERC RNA Levels by qRT-PCR and Telomerase Activity by TRAP in Archival Tumor Tissue and to Explore Association of Telomerase Positivity With Objective Response and PFS
NCT02426086 (22) [back to overview]Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat
NCT02426086 (22) [back to overview]Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat
NCT02426086 (22) [back to overview]Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria
NCT02426086 (22) [back to overview]Elimination Half-Life (t1/2) of Imetelstat
NCT02426086 (22) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Imetelstat
NCT02426086 (22) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT02426086 (22) [back to overview]Overall Survival
NCT02426086 (22) [back to overview]Patient's Global Impression of Change (PGIC)
NCT02426086 (22) [back to overview]Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria
NCT02426086 (22) [back to overview]Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT
NCT02426086 (22) [back to overview]Percentage of Participants With Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-C30): Global Health Status
NCT02426086 (22) [back to overview]Percentage of Participants With Symptom Response
NCT02426086 (22) [back to overview]Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat
NCT02426086 (22) [back to overview]Total Systemic Clearance (CL) of Imetelstat
NCT02426086 (22) [back to overview]Volume of Distribution (Vd) of Imetelstat
NCT02426086 (22) [back to overview]EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS)
NCT02426086 (22) [back to overview]Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria
NCT02426086 (22) [back to overview]Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI)
NCT02426086 (22) [back to overview]Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria
NCT02426086 (22) [back to overview]Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria
NCT02426086 (22) [back to overview]Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria
NCT02426086 (22) [back to overview]Percentage of Participants With Spleen Response

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1

The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD158
Paclitaxel/Carboplatin + Motesanib 125 mg QD525
Paclitaxel/Carboplatin + Motesanib 75 mg BID448
Panitumumab + Motesanib 50 mg QD328
Panitumumab + Motesanib 125 mg QD444
Panitumumab + Motesanib 75 mg BID198
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD360

[back to top]

Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1

Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionμg*hr/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD0.971
Paclitaxel/Carboplatin + Motesanib 125 mg QD3.21
Paclitaxel/Carboplatin + Motesanib 75 mg BID2.91
Panitumumab + Motesanib 50 mg QD1.74
Panitumumab + Motesanib 125 mg QD3.23
Panitumumab + Motesanib 75 mg BID2.04

[back to top]

Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2

Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionμg*hr/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD4.50
Paclitaxel/Carboplatin + Motesanib 75 mg BID3.11
Panitumumab + Motesanib 50 mg QD1.26
Panitumumab + Motesanib 125 mg QD3.92
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD3.16

[back to top]

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.

Interventionhours (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD7.34
Paclitaxel/Carboplatin + Motesanib 125 mg QD5.33
Paclitaxel/Carboplatin + Motesanib 75 mg BID5.77
Panitumumab + Motesanib 50 mg QD6.47
Panitumumab + Motesanib 125 mg QD7.57
Panitumumab + Motesanib 75 mg BID8.28

[back to top]

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD6.41
Paclitaxel/Carboplatin + Motesanib 75 mg BID6.36
Panitumumab + Motesanib 50 mg QD7.08
Panitumumab + Motesanib 125 mg QD4.90

[back to top]

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2

The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD148
Paclitaxel/Carboplatin + Motesanib 125 mg QD748
Paclitaxel/Carboplatin + Motesanib 75 mg BID390
Panitumumab + Motesanib 50 mg QD265
Panitumumab + Motesanib 125 mg QD672
Panitumumab + Motesanib 75 mg BID242
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD651

[back to top]

Percentage of Participants With an Overall Objective Response

Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions. (NCT00094835)
Timeframe: After 9 weeks of treatment (at the end of Cycle 3)

InterventionPercentage of participants (Number)
Paclitaxel/Carboplatin + Motesanib 50 mg QD33
Paclitaxel/Carboplatin + Motesanib 125 mg QD18
Paclitaxel/Carboplatin + Motesanib 75 mg BID0
Panitumumab + Motesanib 50 mg QD0
Panitumumab + Motesanib 125 mg QD0
Panitumumab + Motesanib 75 mg BID0
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD17

[back to top]

Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Median)
Paclitaxel/Carboplatin + Motesanib 50 mg QD0.75
Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0
Paclitaxel/Carboplatin + Motesanib 75 mg BID0.75
Panitumumab + Motesanib 50 mg QD1.5
Panitumumab + Motesanib 125 mg QD1.0
Panitumumab + Motesanib 75 mg BID0.58
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0

[back to top]

Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Median)
Paclitaxel/Carboplatin + Motesanib 50 mg QD1.5
Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0
Paclitaxel/Carboplatin + Motesanib 75 mg BID0.63
Panitumumab + Motesanib 50 mg QD1.0
Panitumumab + Motesanib 125 mg QD0.75
Panitumumab + Motesanib 75 mg BID1.0
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD2.0

[back to top]

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). (NCT00094835)
Timeframe: Cycle 1, Day 3, 24 hours post-dose

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD9.12
Paclitaxel/Carboplatin + Motesanib 125 mg QD26.5
Paclitaxel/Carboplatin + Motesanib 75 mg BID56.7
Panitumumab + Motesanib 50 mg QD14.0
Panitumumab + Motesanib 125 mg QD32.5
Panitumumab + Motesanib 75 mg BID56.8

[back to top]

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). (NCT00094835)
Timeframe: Cycle 2, Day 1, 24 hours post-dose

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD43.4
Paclitaxel/Carboplatin + Motesanib 75 mg BID45.4
Panitumumab + Motesanib 50 mg QD10.4
Panitumumab + Motesanib 125 mg QD61.1
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD45.1

[back to top]

Objective Response Rate

Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by the total number of analyzable patients. CR is defined as complete disappearance of all tumor lesions, and partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. (NCT00427349)
Timeframe: assessed every 8 weeks while on treatment, and frequency of tumor measurements during follow-up were determined by the treating physician, assessed up to 5 years

Interventionpercentage of participants (Number)
AMG 706+Octreotide13.6

[back to top]

Overall Survival

Overall survival (OS) is defined as the time from registration until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method , with 95% confidence intervals calculated using Greenwood's formula (NCT00427349)
Timeframe: assessed every 3 months if patient is < 2 years from study entry, then every 6 months up to 5 years

Interventionmonths (Median)
AMG 706+Octreotide27.5

[back to top]

Four-month Progression-free Survival Rate

Four-month progression-free survival (PFS) rate is defined as number of patients who are still progression free at 4 months after study entry divided by number of eligible and treated patients enrolled to the study. Progression is evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), or unequivocal progression of existing non-target lesions. (NCT00427349)
Timeframe: assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four

Interventionpercentage of participants (Number)
AMG 706+Octreotide78.5

[back to top]

Duration of Overall Survival (OS)

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. (NCT00574951)
Timeframe: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Interventionmonths (Median)
AMG 70613.1

[back to top]

Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0

Number of participants with a maximum grade of 3 or higher during the treatment period. (NCT00574951)
Timeframe: Assessed every cycle while on treatment, 30 days after the last cycle of treatment

InterventionParticipants (Count of Participants)
CardiacGastrointestinalHepatobiliaryMetabolicMuskuloskeletalOther NeurologicalPainPulmonaryDeath, Not CTC coded
AMG 706251414111

[back to top]

Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0

RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. (NCT00574951)
Timeframe: CT scan or MRI every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated up to 5 years.

InterventionParticipants (Count of Participants)
Partial responseComplete response
AMG 70610

[back to top]

Blastic MF/AML Participants: Percentage of Participants With Overall Response

For this pilot study, overall response was defined as achievement of a leukemic response (i.e. a clinically meaningful reduction in Blast cells). This was quantified as <5% peripheral blood and bone marrow blasts % that lasts for at least two months. Data is reported separately for this arm where response was assessed by this specific criterion. (NCT01731951)
Timeframe: Up to first 9 cycles of treatment (each cycle was of 28 days for Arm D)

Interventionpercentage of participants (Number)
Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)0

[back to top]

MDS Participants: Duration of Response Per IWG Criteria

DOR: time of initial response (CR/PR/HI) until documented PD/death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. Data reported separately for arm assessed per IWG. Kaplan-Meier method was used. (NCT01731951)
Timeframe: From the time of initial response (CR/PR/HI) until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)

Interventionmonths (Median)
Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)NA

[back to top]

MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria

Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. HI responses included: 1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of RBC units transfusions by absolute number of >=4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 week. Only RBC transfusions given for Hgb of ≤9.0 g/dL. Data is reported separately for arm assessed as per IWG criteria. (NCT01731951)
Timeframe: Up to approximately 5.7 years

InterventionParticipants (Count of Participants)
Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)3

[back to top]

MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria

OR: HI/PR/CR per IWG. CR: BM:≤5% myeloblasts (all cell lines normal maturation), Peripheral blood:Hgb ≥11g/dL, PLTs ≥100x10^9/L, Neutrophils ≥1.0x10^9/L, Blasts 0%. PR: All CR criteria if abnormal before treatment except- BM blasts decreased ≥50% over pretreatment but still >5%, Cellularity, morphology not relevant. HI responses:1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of red blood cell(RBC) units transfusions by absolute ≥4 RBC transfusions/8 week (wk) compared with pretreatment transfusion number in previous 8 wk. Only RBC transfusions given for Hgb of ≤9.0 g/dL.2)PLTs:Absolute increase ≥30x10^9/L starting >20x10^9/L PLTs; Increase from <20x10^9/L to >20x10^9/L and by ≥100%; 3)Neutrophil: ≥100% increase, absolute increase >0.5x10^9/L; 4)Progression/relapse after HI:≥1 of following:≥50% decrement from maximum response levels in granulocytes/PLTs, Reduction in Hgb ≥1.5 g/dL,Transfusion dependence. Data is reported separately for arm whose response was assessed per IWG. (NCT01731951)
Timeframe: Up to first 9 cycles of treatment (each cycle was of 28 days for Arm G)

Interventionpercentage of participants (Number)
Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)33.3

[back to top]

MDS Participants: Time to Response

Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. Response was defined as HI, PR or CR per IWG criteria. Data for time to response is reported as per criteria of response assessment. (NCT01731951)
Timeframe: From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)

Interventionmonths (Median)
Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)3.7

[back to top]

MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT

Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. Anemia response per IWG-MRT Criteria- Transfusion-independent participants: a ≥20 g/L increase in hemoglobin level. Transfusion-dependent participants: becoming transfusion-independent. Data is reported separately for arms assessed as per the IWG-MRT criteria. (NCT01731951)
Timeframe: Up to approximately 5.7 years

InterventionParticipants (Count of Participants)
Arm A: Imetelstat 9.4 mg/kg (MF)1
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)0
Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)0
Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts])0
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])3

[back to top]

MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria

DOR measured from time of initial response (CR/PR/CI) until documented PD or death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. CR:BM: <5%blasts; ≤Grade 1 MF, AND Peripheral blood:Hb≥100 g/L and = 5 cm below LCM) or increase in severity of anemia, thrombocytopenia or neutropenia. Data is reported separately for arms whose DOR was assessed per IWG-MRT. Kaplan-Meier method was used. (NCT01731951)
Timeframe: From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)

Interventionmonths (Median)
Arm A: Imetelstat 9.4 mg/kg (MF)24.36
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)NA
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])35.52

[back to top]

MF Participants: Percentage of Participants With Overall Response (OR) - (Clinical Improvement[CI] or Partial Remission[PR] or Complete Remission[CR]) Per International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria

OR:CI/PR/CR per IWG-MRT. CR:Bone marrow (BM):<5% blasts;≤Grade 1 MF, AND Peripheral blood:Hemoglobin (Hb) ≥100 g/liter (g/L) and NCT01731951)
Timeframe: Up to first 9 cycles of treatment (each cycle was of 21 days for Arms A and B and 28 days for Arms E and F)

Interventionpercentage of participants (Number)
Arm A: Imetelstat 9.4 mg/kg (MF)36.84
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)35.7
Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts])0
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])33.3

[back to top]

MF Participants: Time to Response

Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. The response CI/CR/PR was assessed by IWG-MRT criteria. (NCT01731951)
Timeframe: From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)

Interventionmonths (Median)
Arm A: Imetelstat 9.4 mg/kg (MF)2.1
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)1.4
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])2.9

[back to top]

Overall Survival (OS)

OS was defined as the as the interval from Study Day 1 to the date of death from any cause. Survival time of living participants was censored on the last date a participant is known to be alive or lost to follow-up. Overall Survival was estimated by Kaplan-Meier method. (NCT01731951)
Timeframe: From Study Day 1 to the date of death from any cause (Up to approximately 5.7 years)

Interventionmonths (Median)
Arm A: Imetelstat 9.4 mg/kg (MF)42.61
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)26.73
Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)4.93
Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts])12.09
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])NA
Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)28.42

[back to top] [back to top]

Number of Participants With Spleen Response Per IWG-MRT Criteria

Spleen response per IWG-MRT criteria defined as baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable, OR A baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%. Baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response. Confirmation by Magnetic resonance imaging (MRI) or computerized tomography (CT) showing ≥35% spleen volume reduction is recommended (but not required). Spleen response was assessed only in participants with MF. (NCT01731951)
Timeframe: Up to approximately 5.7 years

InterventionParticipants (Count of Participants)
Arm A: Imetelstat 9.4 mg/kg (MF)3
Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)1
Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)1
Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts])0
Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])2

[back to top]

Number of Participants With Telomerase Inhibition

This outcome measure is applicable only for the Molecular biology study arm. Telomerase inhibition was assessed in PBMCs and summarised as 'yes-inhibited' vs. 'no inhibition' (NCT01836549)
Timeframe: Up to 30 days

InterventionParticipants (Count of Participants)
Molecular Biology Study5

[back to top]

Numver of Patients With Telomerase-positive Archival Tumors Who Demonstrate at Least 50% Reduction

This outcome measure is for the Molecular biology study only. The assessment was done to identify cases with at least 50% reduction in telomerase activity. (NCT01836549)
Timeframe: Up to 30 days

InterventionParticipants (Count of Participants)
Molecular Biology Study1

[back to top]

Phase II: Stratum-specific Objective Response (CR+PR) Rate

"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR sustained for at least 6 weeks.~For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. Estimated by cumulative incidence functions." (NCT01836549)
Timeframe: 6 months

InterventionParticipants (Count of Participants)
Stratum-A0
Stratum-B0
Stratum-C0
Stratum-D0

[back to top]

Stratum-specific Progression-free Survival (PFS) (Phase II)

Kaplan-Meier estimates of distributions of survival and PFS for all eligible subjects who received at least one dose of imetelstat will be provided separately. (NCT01836549)
Timeframe: Up to 2 years, from the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure, assessed up to 3 years

Interventiondays (Mean)
Stratum-A30
Stratum-B54.2
Stratum-C50.3
Stratum-D52.6

[back to top]

Number of Patients With Telomerase Expression Data by Detection of hTERT mRNA and TERC RNA Levels by qRT-PCR and Telomerase Activity by TRAP in Archival Tumor Tissue and to Explore Association of Telomerase Positivity With Objective Response and PFS

This secondary objective is for Stratum-B and C only, which enroll HGG and ependymoma patients. We will describe the evidence of telomerase expression by detection of hTERT mRNA and TERC RNA levels by qRT-PCR and telomerase activity by TRAP in archival tumor tissue; Association of telomerase positivity with objective response and PFS will not be able to be conducted as the study was terminated early and there was no objective response. (NCT01836549)
Timeframe: Up to 30 days. Due to small number of patients evaluable for this objective, we can only provide number of patients with the targetted markers as no analysis with PFS is possible.

InterventionParticipants (Count of Participants)
TRAPTERTTERC
Stratum-C333

[back to top]

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

Interventionμg*hr/mL (Mean)
PK: Imetelstat 4.7 mg/kg171
PK: Imetelstat 9.4 mg/kg501

[back to top]

Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

Interventionμg*h/mL (Mean)
PK: Imetelstat 4.7 mg/kg193
PK: Imetelstat 9.4 mg/kg524

[back to top]

Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria

Duration of response (PR/CI/RWCI) is the duration from the date of initial documentation of a response to date of first documented evidence of PD or death, whichever occurs first. PR: BM: normocellular: <5% blasts ≤Grade 1 fibrosis/not meeting BM remission criteria; IMC in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL- ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI/not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, neutropenia. RWCI: Participants who met criteria for response but had worsening cytopenias. PD: Splenomegaly requires MRI showing ≥25% increase in spleen volume. (NCT02426086)
Timeframe: From date of initial documentation of a response to the date of first documented evidence of PD or death, whichever occurs first (approximately up to 2.3 years)

Interventionweeks (Median)
Imetelstat 4.7 mg/kg36.3
Imetelstat 9.4 mg/kg38.3

[back to top]

Elimination Half-Life (t1/2) of Imetelstat

Elimination half-life (t 1/2) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). (NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

Interventionhr (Mean)
PK: Imetelstat 4.7 mg/kg4.6
PK: Imetelstat 9.4 mg/kg5.5

[back to top]

Maximum Observed Plasma Concentration (Cmax) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

Interventionμg/mL (Mean)
PK: Imetelstat 4.7 mg/kg57.0
PK: Imetelstat 9.4 mg/kg81.9

[back to top]

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were AEs with onset during or after the first dose of study drug, and within 30 days following the last dose of study drug. (NCT02426086)
Timeframe: Up to end of extension phase (approximately up to 4.2 years)

InterventionParticipants (Count of Participants)
Imetelstat 4.7 mg/kg47
Imetelstat 9.4 mg/kg59

[back to top]

Overall Survival

Overall Survival is measured from the date of Cycle 1, Day 1 to the date of the participants death. If the participant's was alive or the vital status was unknown, OS was censored at the date that the participant is last known to be alive. (NCT02426086)
Timeframe: Day 1 of Cycle 1 (each cycle was of 21 days), up to the date of the participant's death (approximately up to 4.1 years)

Interventionmonths (Median)
Imetelstat 4.7 mg/kg19.91
Imetelstat 9.4 mg/kg28.09

[back to top]

Patient's Global Impression of Change (PGIC)

The PGIC was used to capture the participant's perspective of improvement or decline in MF symptoms over time. The PGIC had a 7-point response scale ranging from 1 to 7 where, (1=very much improved, 2= somewhat improved, 3= a little improved, 4=no change, 5= a little worse, 6= somewhat worse, 7=very much worse). (NCT02426086)
Timeframe: At the end of treatment, up to approximately 2.3 years

Interventionscore on a scale (Mean)
Imetelstat 4.7 mg/kg4.82
Imetelstat 9.4 mg/kg3.97

[back to top]

Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria

CI per the modified 2013 IWG-MRT criteria defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia (Increase in severity of anemia constitutes the occurrence of new transfusion dependency or a ≥ 2.0 g/dL decrease in hemoglobin level from pretreatment baseline that lasts for at least 12 weeks. Increase in severity of thrombocytopenia or neutropenia is defined as a 2-grade decline, from pretreatment baseline, in platelet count or ANC, according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. In addition, assignment to CI requires a minimum platelet count of ≥ 25,000*10^9/L and ANC of ≥ 0.5*10^9/L.) For all response categories, benefit must last for >12 weeks to qualify as a response. (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg16.7
Imetelstat 9.4 mg/kg25.4

[back to top]

Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT

Clinical response rate (CRR) was defined as percentage of participants who achieved CR, PR, or CI per modified 2013 IWG-MRT criteria. CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in PB: <2%; Hb: 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen: not palpable and ≤350ml volume; EMH: no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, or neutropenia. (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg16.7
Imetelstat 9.4 mg/kg27.1

[back to top]

Percentage of Participants With Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-C30): Global Health Status

EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients. The EORTC QLQ-C30 included 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) which are based on 4-point scale (1= Not at all to 4= Very much); and 1 global health status scale based on 7-point scale (1= Very poor to 7= Excellent). All scales and items are averaged, transformed to 0-100 scale; higher score=better level of functioning. Clinically meaningful improvement defined as change greater than half of the standard deviation at baseline in QLQ-C30 Global Health Status. (NCT02426086)
Timeframe: Up to end of the treatment (approximately up to 2.3 years)

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg22.2
Imetelstat 9.4 mg/kg36.4

[back to top]

Percentage of Participants With Symptom Response

Symptom response rate is defined as percentage of participants who achieved ≥ 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary. The MFSAF assessed following symptoms due to Myelofibrosis (MF): night sweats, itchiness, abdominal discomfort, pain under ribs on left side, feeling of fullness, bone or muscle pain and degree of inactivity. Each item is scored on a scale of 0 (absent) to 10 (worst imaginable) with higher scores indicating more severe symptoms and greater inactivity. The total score ranges from 0-70, where 0 indicates absent/as good as it can be and 70 indicates worst imaginable/as bad as it can be. (NCT02426086)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg6.3
Imetelstat 9.4 mg/kg32.2

[back to top]

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

Interventionhr (Median)
PK: Imetelstat 4.7 mg/kg2.00
PK: Imetelstat 9.4 mg/kg2.00

[back to top]

Total Systemic Clearance (CL) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

InterventionL/hr/kg (Mean)
PK: Imetelstat 4.7 mg/kg0.0329
PK: Imetelstat 9.4 mg/kg0.0252

[back to top]

Volume of Distribution (Vd) of Imetelstat

(NCT02426086)
Timeframe: 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days)

InterventionL/kg (Mean)
PK: Imetelstat 4.7 mg/kg0.198
PK: Imetelstat 9.4 mg/kg0.190

[back to top]

EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS)

EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. (NCT02426086)
Timeframe: At the end of treatment, up to approximately 2.3 years

,
Interventionscore on a scale (Mean)
EQ-5D-5L: Utility ScoreEQ-5D-5L: VAS
Imetelstat 4.7 mg/kg0.49851.28
Imetelstat 9.4 mg/kg0.62647.73

[back to top]

Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria

"Anemia response per modified 2013 IWG-MRT criteria. Anemia response is defined as participants with baseline Hb <10 g/dL but not meeting strict criteria for transfusion dependency: a ≥ 2 g/dL increase in Hb; Transfusion dependent participants at baseline: becoming transfusion independent. Transfusion independence is defined as absence of any pRBC transfusions for at least 12 rolling weeks. For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for anemia response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia." (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

,
Interventionpercentage of participants (Number)
Anemia response with CIAnemia response without CI
Imetelstat 4.7 mg/kg4.20
Imetelstat 9.4 mg/kg6.81.7

[back to top]

Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI)

The BPI rates the intensity of pain on 4 items (right now, worst, least, and average), and the interference in 7 areas (general activity, mood, walking ability, normal work, relations, sleep, enjoyment of life). Minimum value = 0; maximum value = 10. Higher scores indicate greater symptom severity/worse outcomes. Clinically meaningful improvement in BPI defined as change greater than half of the standard deviation at baseline. (NCT02426086)
Timeframe: Up to end of treatment (approximately up to 2.3 years)

,
Interventionpercentage of participants (Number)
Pain at its Worst: ImprovementPain at its Least: ImprovementPain on the Average: ImprovementPain Right Now: ImprovementRelief Pain Treatments Provided: ImprovementPain Interfered General Activity: ImprovementPain Interfered with Mood: ImprovementPain Interfered Walking Ability: ImprovementPain Interfered with Normal Work: ImprovementPain Interfered with Relations: ImprovementPain Interfered with Sleep: ImprovementPain Interfered Enjoyment of Life: Improvement
Imetelstat 4.7 mg/kg50.044.455.661.150.072.250.038.961.144.461.161.1
Imetelstat 9.4 mg/kg75.851.566.766.753.168.859.478.162.553.178.162.5

[back to top]

Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria

Spleen response per modified 2013 IWG-MRT criteria. Spleen response: a baseline splenomegaly that is palpable at 5-10 cm, below the left costal margin (LCM), becomes not palpable or a baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%; A spleen response requires confirmation by MRI showing >35% spleen volume reduction (SVR). For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for spleen response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

,
Interventionpercentage of participants (Number)
Spleen response with CISpleen response without CI
Imetelstat 4.7 mg/kg02.1
Imetelstat 9.4 mg/kg3.40

[back to top]

Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria

Overall Response Rate: % of participants with complete remission (CR) or partial remission (PR) per modified IWG-MRT.CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in peripheral blood (PB):<2%;hemoglobin (Hb):10 g/dL-upper limit of normal (ULN); neutrophils:1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen:not palpable and ≤350ml volume; extramedullary hematopoiesis (EMH): no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH;symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. All response categories, benefit must last >12 weeks to qualify as response. (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg0
Imetelstat 9.4 mg/kg1.7

[back to top]

Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria

Symptoms response per modified 2013 IWG-MRT criteria. Symptoms Response: a ≥50% reduction in the modified MFSAF v2.0 TSS. For response category, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for symptom response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. (NCT02426086)
Timeframe: Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

,
Interventionpercentage of participants (Number)
Symptom response with CISymptom response without CI
Imetelstat 4.7 mg/kg14.64.2
Imetelstat 9.4 mg/kg22.08.5

[back to top]

Percentage of Participants With Spleen Response

Spleen response rate is defined as the percentage of participants who achieved ≥ 35% reduction in spleen volume at Week 24 from baseline performed by the IRC using magnetic resonance imaging (MRI). (NCT02426086)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Imetelstat 4.7 mg/kg0
Imetelstat 9.4 mg/kg10.2

[back to top]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
glycine
[no description available]		2.2510alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		17.959733pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
acetazolamide
Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)		2.1310monocarboxylic acid amide;
sulfonamide;
thiadiazoles		anticonvulsant;
diuretic;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
deferoxamine
Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator.		2.1310acyclic desferrioxaminebacterial metabolite;
ferroptosis inhibitor;
iron chelator;
siderophore
valproic acid
Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.		3.1710branched-chain fatty acid;
branched-chain saturated fatty acid		anticonvulsant;
antimanic drug;
EC 3.5.1.98 (histone deacetylase) inhibitor;
GABA agent;
neuroprotective agent;
psychotropic drug;
teratogenic agent
dup 697
DuP 697: structure given in first source		2.1310thiophenes
fluorouracil
Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.		5.9121nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
ketoconazole
1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.		3.4311dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine
vorinostat
Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.. vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).		3.1710dicarboxylic acid diamide;
hydroxamic acid		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
thalidomide
Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.		4.1320phthalimides;
piperidones
pyrroles
1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.		7.22130pyrrole;
secondary amine
thiophenes
Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring.		2.1310mancude organic heteromonocyclic parent;
monocyclic heteroarene;
thiophenes;
volatile organic compound		non-polar solvent
quinazolines
Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.		9.74151azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinazolines
indazoles
Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.		6.81100indazole
thiazoles
[no description available]		4.34301,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
pyrazines
Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.		3.1710diazine;
pyrazines		Daphnia magna metabolite
azacitidine
Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.		3.3110N-glycosyl-1,3,5-triazine;
nucleoside analogue		antineoplastic agent
alpha-aminopyridine
alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.		2.1110
deoxycytidine
[no description available]		6.7232pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
vidarabine
adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond.		2.0810beta-D-arabinoside;
purine nucleoside		antineoplastic agent;
bacterial metabolite;
nucleoside antibiotic
camptothecin
NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source		5.9121delta-lactone;
pyranoindolizinoquinoline;
quinoline alkaloid;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
genotoxin;
plant metabolite
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		11.491411taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
etoposide
[no description available]		2.4110beta-D-glucoside;
furonaphthodioxole;
organic heterotetracyclic compound		antineoplastic agent;
DNA synthesis inhibitor
gemcitabine
gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.		5.3222organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic
irinotecan
[no description available]		3.1910carbamate ester;
delta-lactone;
N-acylpiperidine;
pyranoindolizinoquinoline;
ring assembly;
tertiary alcohol;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
prodrug
capecitabine
Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.		3.1910carbamate ester;
cytidines;
organofluorine compound		antimetabolite;
antineoplastic agent;
prodrug
combretastatin
combretastatin: cytotoxic principle from South African tree COMBRETUM caffrum; structure given in first source; acts at COLCHICINE site of TUBULIN		3.1710
ecteinascidin 743
[no description available]		3.1310acetate ester;
azaspiro compound;
bridged compound;
hemiaminal;
isoquinoline alkaloid;
lactone;
organic heteropolycyclic compound;
organic sulfide;
oxaspiro compound;
polyphenol;
tertiary amino compound		alkylating agent;
angiogenesis modulating agent;
anti-inflammatory agent;
antineoplastic agent;
marine metabolite
imatinib mesylate
imatinib methanesulfonate : A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.		9.7493methanesulfonate saltanticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
tyrosine kinase inhibitor
gefitinib
[no description available]		4.6930aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
quinazolines;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
epidermal growth factor receptor antagonist
vadimezan
vadimezan : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 5,6-dimethyl-9-oxoxanthen-4-yl group.		3.1410monocarboxylic acid;
xanthones		antineoplastic agent
docetaxel anhydrous
Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.		4.7821secondary alpha-hydroxy ketone;
tetracyclic diterpenoid		antimalarial;
antineoplastic agent;
photosensitizing agent
vatalanib
[no description available]		5.760monochlorobenzenes;
phthalazines;
pyridines;
secondary amino compound		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
vascular endothelial growth factor receptor antagonist
birb 796
[no description available]		2.1110aromatic ether;
morpholines;
naphthalenes;
pyrazoles;
ureas		EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
immunomodulator
erlotinib hydrochloride
[no description available]		4.3711hydrochloride;
terminal acetylenic compound		antineoplastic agent;
protein kinase inhibitor
sorafenib
[no description available]		7.51150(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide		angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
lenalidomide
[no description available]		4.1320aromatic amine;
dicarboximide;
isoindoles;
piperidones		angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
bortezomib
[no description available]		3.1710amino acid amide;
L-phenylalanine derivative;
pyrazines		antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
carboplatin
[no description available]		10.79109
decitabine
[no description available]		3.31102'-deoxyribonucleoside
s 1033
[no description available]		4.0520(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
fludarabine
[no description available]		2.0810purine nucleoside
alpha-2'-deoxythioguanosine
alpha-2'-deoxythioguanosine: structure		2.4110
e 7010
E 7010: inhibits tubulin polymerization; structure given in first source		3.1410sulfonamide
dasatinib
N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1,3-thiazole-5-carboxamide: a dasatinib prodrug; structure in first source. dasatinib (anhydrous) : An aminopyrimidine that is 2-methylpyrimidine which is substituted at position 4 by the primary amino group of 2-amino-1,3-thiazole-5-carboxylic acid and at position 6 by a 4-(2-hydroxyethyl)piperazin-1-yl group, and in which the carboxylic acid group has been formally condensed with 2-chloro-6-methylaniline to afford the corresponding amide. A multi-targeted kinase inhibitor, it is used, particularly as the monohydrate, for the treatment of chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia. Note that the name 'dasatinib' is used to refer to the monohydrate (USAN) as well as to anhydrous dasatinib (INN).		3.13101,3-thiazoles;
aminopyrimidine;
monocarboxylic acid amide;
N-(2-hydroxyethyl)piperazine;
N-arylpiperazine;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
zd 6474
CH 331: structure in first source		6.9110aromatic ether;
organobromine compound;
organofluorine compound;
piperidines;
quinazolines;
secondary amine		antineoplastic agent;
tyrosine kinase inhibitor
sirolimus
Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.		3.1310antibiotic antifungal drug;
cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
organic heterotricyclic compound;
secondary alcohol		antibacterial drug;
anticoronaviral agent;
antineoplastic agent;
bacterial metabolite;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source. alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group.		2.11101,4-benzoquinones;
ansamycin;
carbamate ester;
secondary amino compound;
tertiary amino compound		Hsp90 inhibitor
su 11248
[no description available]		7.22130monocarboxylic acid amide;
pyrroles		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
everolimus
[no description available]		3.1310cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
primary alcohol;
secondary alcohol		anticoronaviral agent;
antineoplastic agent;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
axitinib
[no description available]		6.6290aryl sulfide;
benzamides;
indazoles;
pyridines		antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
tanespimycin
CP 127374: analog of herbimycin A		3.17101,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound		antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
staurosporine
staurosporinium : Conjugate acid of staurosporine.		4.0520ammonium ion derivative
lenvatinib
lenvatinib : A member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine.		4.120aromatic amide;
aromatic ether;
cyclopropanes;
monocarboxylic acid amide;
monochlorobenzenes;
phenylureas;
quinolines		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist;
orphan drug;
vascular endothelial growth factor receptor antagonist
midostaurin
midostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.		4.0520benzamides;
gamma-lactam;
indolocarbazole;
organic heterooctacyclic compound		antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
cediranib
[no description available]		5.8860aromatic ether
masitinib
[no description available]		3.14101,3-thiazoles;
benzamides;
N-alkylpiperazine;
pyridines		antineoplastic agent;
antirheumatic drug;
tyrosine kinase inhibitor
pazopanib
pazopanib: a protein kinase inhibitor. pazopanib : A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.		5.8960aminopyrimidine;
indazoles;
sulfonamide		angiogenesis modulating agent;
antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
bibw 2992
[no description available]		3.1510aromatic ether;
enamide;
furans;
monochlorobenzenes;
organofluorine compound;
quinazolines;
secondary carboxamide;
tertiary amino compound		antineoplastic agent;
tyrosine kinase inhibitor
regorafenib
[no description available]		3.1910(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
phenylureas;
pyridinecarboxamide		antineoplastic agent;
hepatotoxic agent;
tyrosine kinase inhibitor
fg-4592
roxadustat: structure in first source. roxadustat : An N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylic acid. It is an inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH).		2.2510aromatic ether;
isoquinolines;
N-acylglycine		EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor;
EC 1.14.11.29 (hypoxia-inducible factor-proline dioxygenase) inhibitor
chir-265
[no description available]		2.1110aromatic ether
oligonucleotides
[no description available]		18.5311936
fedratinib
fedratinib: a selective small-molecule inhibitor of JAK2		3.3510sulfonamide
n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide: a Janus kinase 1 and Janus kinase 2 inhibitor; structure in first source. momelotinib : A benzamide obtained by formal condensation of the carboxy group of 4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzoic acid with the primary amino group of aminoacetonitrile. It is an ATP-competitive JAK1/JAK2 inhibitor with IC50 of 11 nM and 18 nM, respectively. Used for the treatment of patients with intermediate- or high-risk myelofibrosis.		2.1510aminopyrimidine;
benzamides;
morpholines;
nitrile;
secondary amino compound;
tertiary amino compound		anti-anaemic agent;
antineoplastic agent;
apoptosis inducer;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
cabozantinib
cabozantinib: a multikinase inhibitor. cabozantinib : A dicarboxylic acid diamide that is N-phenyl-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in which the hydrogen at position 4 on the phenyl ring is substituted by a (6,7-dimethoxyquinolin-4-yl)oxy group. A multi-tyrosine kinase inhibitor, used (as its malate salt) for the treatment of progressive, metastatic, medullary thyroid cancer.		4.430aromatic ether;
dicarboxylic acid diamide;
organofluorine compound;
quinolines		antineoplastic agent;
tyrosine kinase inhibitor
incb-018424
[no description available]		5.4531nitrile;
pyrazoles;
pyrrolopyrimidine		antineoplastic agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
piperidines
Piperidines: A family of hexahydropyridines.		7.07120
interleukin-8
Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.		2.1710
abt-348
ilorasertib: an antineoplastic agent and protein kinase inhibitor; structure in first source		2.1110
abt-199
venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.. venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.		3.3110aromatic ether;
C-nitro compound;
monochlorobenzenes;
N-alkylpiperazine;
N-arylpiperazine;
N-sulfonylcarboxamide;
oxanes;
pyrrolopyridine		antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
grn163
GRN163: inhibitor of telomerase RNA in human multiple myeloma cells.		3.1510
ceritinib
ceritinib: an anaplastic lymphoma kinase inhibitor. ceritinib : A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the treatment of ALK-positive metastatic non-small cell lung cancer.		2.4110aminopyrimidine;
aromatic ether;
organochlorine compound;
piperidines;
secondary amino compound;
sulfone		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
levoleucovorin
Levoleucovorin: A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.. (6S)-5-formyltetrahydrofolic acid : The pharmacologically active (6S)-stereoisomer of 5-formyltetrahydrofolic acid.		4.41115-formyltetrahydrofolic acidantineoplastic agent;
metabolite
nintedanib
nintedanib : A member of the class of oxindoles that is a kinase inhibitor used (in the form of its ethylsulfonate salt) for the treatment of idiopathic pulmonary fibrosis and cancer.		4.0920
ConditionIndicatedRelationship StrengthStudiesTrials
Agnogenic Myeloid Metaplasia
[description not available]		08.8763
Primary Myelofibrosis
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.		08.8763
Neuroblastoma
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)		08.9521
Hematologic Malignancies
[description not available]		02.2110
Myeloproliferative Disorders
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.		04.6850
Hematologic Neoplasms
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.		02.2110
Hemorrhagic Thrombocythemia
[description not available]		07.8452
Thrombocythemia, Essential
A clinical syndrome characterized by repeated spontaneous hemorrhages and a remarkable increase in the number of circulating platelets.		07.8452
Dysmyelopoietic Syndromes
[description not available]		06.5951
Anemia
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.		03.830
Myelodysplastic Syndromes
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.		011.5951
Thrombopenia
[description not available]		02.2510
Thrombocytopenia
A subnormal level of BLOOD PLATELETS.		02.2510
Minimal Disease, Residual
[description not available]		02.5120
Erythremia
[description not available]		05.7821
Polycythemia Vera
A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.		05.7821
Thrombocythemia
[description not available]		02.8330
Myeloproliferative-Myelodisplastic Diseases
[description not available]		02.3110
Myelodysplastic-Myeloproliferative Diseases
Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.		02.3110
Recrudescence
[description not available]		04.8721
Acute Lymphoid Leukemia
[description not available]		02.3110
Precursor Cell Lymphoblastic Leukemia-Lymphoma
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.		02.3110
Altitude Hypoxia
Low ambient oxygen tension associated with ALTITUDE.		02.1310
Brain Swelling
[description not available]		02.1310
Altitude Sickness
Multiple symptoms associated with reduced oxygen at high ALTITUDE.		02.1310
Brain Edema
Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)		02.1310
Carcinoma, Non-Small Cell Lung
[description not available]		013.092312
Cancer of Lung
[description not available]		013.092312
Local Neoplasm Recurrence
[description not available]		07.1775
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		013.092312
Lung Neoplasms
Tumors or cancer of the LUNG.		013.092312
Benign Neoplasms
[description not available]		011.57168
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		011.57168
Leukemia, Lymphocytic
[description not available]		02.0810
Chromosome Deletion
Actual loss of portion of a chromosome.		02.0810
Leukemia, Lymphoid
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.		02.0810
Bone Cancer
[description not available]		03.4711
Ewing Sarcoma
[description not available]		03.4711
Bone Neoplasms
Tumors or cancer located in bone tissue or specific BONES.		03.4711
Sarcoma, Ewing
A malignant tumor of the bone which always arises in the medullary tissue, occurring more often in cylindrical bones. The tumor occurs usually before the age of 20, about twice as frequently in males as in females.		03.4711
Diarrhea
An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.		04.411
Colorectal Cancer
[description not available]		06.741
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		06.741
Angiogenesis, Pathologic
[description not available]		05.1250
Carcinogenesis
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.		02.110
Benign Neoplasms, Brain
[description not available]		03.9240
Anaplastic Ependymoma
[description not available]		02.110
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		03.9240
Ependymoma
Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9)		02.110
Carcinoma, Epidermoid
[description not available]		05.2941
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		05.2941
Hemoptysis
Expectoration or spitting of blood originating from any part of the RESPIRATORY TRACT, usually from hemorrhage in the lung parenchyma (PULMONARY ALVEOLI) and the BRONCHIAL ARTERIES.		04.411
Choroid Neovascularization
[description not available]		02.1110
Rhabdoid Tumor
A rare but highly lethal childhood tumor found almost exclusively in infants. Histopathologically, it resembles RHABDOMYOSARCOMA but the tumor cells are not of myogenic origin. Although it arises primarily in the kidney, it may be found in other parts of the body. The rhabdoid cytomorphology is believed to be the expression of a very primitive malignant cell. (From Holland et al., Cancer Medicine, 3d ed, p2210)		02.110
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		03.1950
Acute Myelogenous Leukemia
[description not available]		02.110
Leukemia, Myeloid, Acute
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.		02.110
Anoxemia
[description not available]		02.1110
Pulmonary Hypertension
[description not available]		02.1110
Hypoxia
Sub-optimal OXYGEN levels in the ambient air of living organisms.		02.1110
Hypertension, Pulmonary
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.		02.1110
Cancer of the Thyroid
[description not available]		011.8176
Thyroid Neoplasms
Tumors or cancer of the THYROID GLAND.		011.8176
Breast Cancer
[description not available]		011.552
Breast Neoplasms
Tumors or cancer of the human BREAST.		06.552
Glial Cell Tumors
[description not available]		03.9121
Glioma
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)		03.9121
Osteogenic Sarcoma
[description not available]		02.1110
Osteosarcoma
A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)		07.1110
Astrocytoma, Grade IV
[description not available]		02.4820
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		02.4820
Cirrhosis
[description not available]		04.4111
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.		09.4111
Carcinoma, Neuroendocrine
A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round blue cells, granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small (oat) cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)		03.7130
Refractory Anemia
[description not available]		07.1310
Anemia, Sideroblastic
Anemia characterized by the presence of erythroblasts containing excessive deposits of iron in the marrow.		02.1310
Anemia, Refractory
A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.		02.1310
Innate Inflammatory Response
[description not available]		03.0410
Inflammation
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.		03.0410
Central Nervous System Neoplasm
[description not available]		03.5111
Central Nervous System Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.		03.5111
Acute Edematous Pancreatitis
[description not available]		02.1310
Cholangitis
Inflammation of the biliary ductal system (BILE DUCTS); intrahepatic, extrahepatic, or both.		02.1310
Pancreatitis
INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.		02.1310
Esophageal Squamous Cell Carcinoma
A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.		07.1510
Cancer of Esophagus
[description not available]		02.5120
Esophageal Neoplasms
Tumors or cancer of the ESOPHAGUS.		02.5120
Polyploid
[description not available]		02.1510
Adenoma, Oxyphilic
A usually benign glandular tumor composed of oxyphil cells, large cells with small irregular nuclei and dense acidophilic granules due to the presence of abundant MITOCHONDRIA. Oxyphil cells, also known as oncocytes, are found in oncocytomas of the kidney, salivary glands, and endocrine glands. In the thyroid gland, oxyphil cells are known as Hurthle cells and Askanazy cells.		07.4744
Follicular Thyroid Carcinoma
[description not available]		07.6554
Carcinoma, Papillary
A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)		08.5754
Adenocarcinoma, Follicular
An adenocarcinoma of the thyroid gland, in which the cells are arranged in the form of follicles. (From Dorland, 27th ed)		07.6554
Neoplasms, Pleural
[description not available]		02.0510
Carcinoma, Thymic
[description not available]		02.0510
Cancer of the Thymus
[description not available]		02.0510
Thymoma
A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)		02.0510
Thymus Neoplasms
Tumors or cancer of the THYMUS GLAND.		02.0510
Disease Exacerbation
[description not available]		03.3620
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.0510
Experimental Mammary Neoplasms
[description not available]		02.0510
Carcinoma, Medullary
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)		07.2142
Gastrointestinal Stromal Neoplasm
[description not available]		010.17105
Gastrointestinal Stromal Tumors
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).		010.17105
Cancer of Prostate
[description not available]		03.3820
Prostatic Neoplasms
Tumors or cancer of the PROSTATE.		03.3820
Colonic Inertia
Symptom characterized by the passage of stool once a week or less.		03.4411
Lassitude
[description not available]		03.4411
Constipation
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.		03.4411
Fatigue
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.		03.4411
Nausea
An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.		05.3322
Cancer of Head
[description not available]		02.0510
Head and Neck Neoplasms
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)		02.0510
Cancer of Pancreas
[description not available]		02.0510
Pancreatic Neoplasms
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).		02.0510
Metastase
[description not available]		04.7721
Neoplasm Metastasis
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.		04.7721
Deep Vein Thrombosis
[description not available]		04.3711
Blood Pressure, High
[description not available]		05.7822
Emesis
[description not available]		04.3711
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		05.7822
Vomiting
The forcible expulsion of the contents of the STOMACH through the MOUTH.		04.3711
Venous Thrombosis
The formation or presence of a blood clot (THROMBUS) within a vein.		04.3711
Adenocarcinoma, Basal Cell
[description not available]		04.7821
Adenocarcinoma
A malignant epithelial tumor with a glandular organization.		04.7821
Female Genital Neoplasms
[description not available]		02.9910
Hepatocellular Carcinoma
[description not available]		02.9910
Cancer of Liver
[description not available]		02.9910
Genital Neoplasms, Female
Tumor or cancer of the female reproductive tract (GENITALIA, FEMALE).		02.9910
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.		02.9910
Liver Neoplasms
Tumors or cancer of the LIVER.		02.9910
Cancer of Ovary
[description not available]		03.4711
Peritoneal Carcinomatosis
[description not available]		03.4711
Cancer of the Fallopian Tube
[description not available]		03.4711
Fallopian Tube Neoplasms
Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.		03.4711
Ovarian Neoplasms
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.		03.4711
Peritoneal Neoplasms
Tumors or cancer of the PERITONEUM.		03.4711
Leukemia, Megakaryocytic
[description not available]		02.0310
Leukemia, Megakaryoblastic, Acute
An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.		02.0310
Carcinoma, Anaplastic
[description not available]		02.9610
Carcinoma
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for cancer.		02.9610