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Report for Clinical Trial NCT00335868

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy

RATIONALE: PHA-739358 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well PHA-739358 works in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.

NCT00335868 Leukemia
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

3 Interventions

Name: danusertib

Type: Drug

Name: laboratory biomarker analysis

Type: Other

Name: pharmacological study

Type: Other


Primary Outcomes

Measure: Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase

Measure: Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities

Measure: Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing

Measure: Changes in histone H3 and CRKL phosphorylation

Measure: Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response

Measure: Complete, partial, or minor cytogenetic response in bone marrow

Purpose: Treatment


There is one SNP

SNPs


1 T315I

DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive OBJECTIVES: - Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy. --- T315I ---

DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive OBJECTIVES: - Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy. --- T315I --- --- T315I ---

- Explore response depending on status of T315I mutation in BCR-ABL kinase. --- T315I ---



HPO Nodes


HPO:
Chronic myelogenous leukemia
Genes 9
KIT MPL ASXL1 TET2 ABL1 JAK2 THPO BCR SRSF2
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Myeloid leukemia
Genes 20
KIT SETBP1 NF1 ARHGAP26 CBL TET2 KRAS PTPN11 F13A1 SAMD9L SAMD9L GATA2 CBL ASXL1 DNMT3A F13B NRAS SRSF2 TERC TERT