SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02081378

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase I, Multicenter, Open-label Study of Oral ABL001 in Patients With Chronic Myelogenous Leukemia (CML) or Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)

The design of a phase I, open label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent ABL001 in CML and Ph+ ALL patients who are relapsed or refractory to or are intolerant of TKIs, and of ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib in Ph positive CML patients who are relapsed or refractory to TKIs.

NCT02081378 Chronic Myelogenous Leukemia Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
MeSH: Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Philadelphia Chromosome
HPO: Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia

5 Interventions

Name: ABL001

Description: ABL001 will be administered orally in a dose escalation schedule.

Type: Drug

ABL001 in CML patients

Name: ABL001 + Nilotinib

Description: ABL001 and Nilotinib will be administered orally in CML patients

Type: Drug

ABL001+Nilotinib in CML patients

Name: ABL001

Description: ABL001 will be administered orally in Ph+ ALL patients

Type: Drug

ABL001 in Ph+ ALL patients

Name: ABL001+imatinib

Description: ABL001 and imatinib will be administered orally in CML patients

Type: Drug

ABL001+Imatinib in CML patients

Name: ABL001+dasatinib

Description: ABL001+dasatinib will be administered orally in CML patients

Type: Drug

ABL001+dasatinib in CML patients


Primary Outcomes

Description: Determine the MTD and/or RDE of ABL001 as single agent in CML and Ph+ ALL, and in combination with either nilotinib or imatinib or dasatinib in CML patients

Measure: Incidence of dose limiting toxicities (DLTs) during the first cycle of study treatment

Time: First Cycle is 28 days

Secondary Outcomes

Measure: Hematologic Response

Time: At screening and first day of cycle 2 and 3 and every 12 weeks afterwards

Measure: Cytogenetic response

Time: at screening or when a patient's BCR-ABL ratio has risen to >1%

Measure: BCR-ABL transcript level

Time: At screening and first day of cycle 2 and 3 and every 12 weeks afterwards

Measure: Cmax of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: Cmin of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: AUCinf of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: AUClast of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: AUCtau of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: T1/2 of ABL001 as measured in plasma

Time: Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.

Measure: Adverse events

Time: Collected from screening visit through post-treatment follow-up period

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 T315I

Inclusion Criteria: For CML patients either: - a. Patients with Ph+ CML in chronic or accelerated phase who were previously treated with at least two different tyrosine kinase inhibitors prior to study entry and are relapsed, refractory to or intolerant of TKIs as determined by investigators or - b. Patients with CML in chronic or accelerated phase who exhibit relapsed disease associated with the presence of the T315I "gatekeeper mutation" after at least one TKI are also eligible provided that no other effective therapy exists For ALL and CML-BP patients: - Patients with CML BP or Ph+ ALL who have a cytopathologically confirmed diagnosis and are relapsed or refractory to at least one prior TKI or intolerant of TKIs. --- T315I ---

At least four weeks must have elapsed since prophylactic CNS irradiation given as part of a front-line therapy regimen for ALL - Major surgery within 2 weeks before the first dose of study treatment Other protocol-defined inclusion/exclusion criteria may apply Inclusion Criteria: For CML patients either: - a. Patients with Ph+ CML in chronic or accelerated phase who were previously treated with at least two different tyrosine kinase inhibitors prior to study entry and are relapsed, refractory to or intolerant of TKIs as determined by investigators or - b. Patients with CML in chronic or accelerated phase who exhibit relapsed disease associated with the presence of the T315I "gatekeeper mutation" after at least one TKI are also eligible provided that no other effective therapy exists For ALL and CML-BP patients: - Patients with CML BP or Ph+ ALL who have a cytopathologically confirmed diagnosis and are relapsed or refractory to at least one prior TKI or intolerant of TKIs. --- T315I ---



HPO Nodes


HPO:
Chronic myelogenous leukemia
Genes 5
MPL BCR JAK2 KIT THPO
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Lymphoid leukemia
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS