Clinical Trials /

BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML)

NCT03127735

Description:

To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03127735

Trial Eligibility

Document

Title

  • Brief Title: BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML)
  • Official Title: An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated and / or Recommended Phase II Dose of Oral Mutant IDH1 (mIDH1) Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Efficacy in Patients With mIDH1-R132X Advanced Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 19036
  • SECONDARY ID: 2016-004095-22
  • NCT ID: NCT03127735

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
BAY1436032BAY1436032

Purpose

To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)

Trial Arms

NameTypeDescriptionInterventions
BAY1436032ExperimentalDose escalation: Various doses of study drug will be tested on a small number of patients/dose with the goal of identifying the most appropriate dose(s) for further evaluation in dose expansion. The MTD of the study drug may or may not be identified. It is anticipated that 3-4 patients will be treated at each dose of study drug to be tested and that 15-20 total patients will be treated in this part of the trial. Dose expansion: Up to 2 different doses of study drug will be tested on up to 30 patients/dose with the goal of identifying the most appropriate RP2D for further clinical development. The doses to be evaluated in this part of the trial will be selected based on information obtained during dose escalation.
  • BAY1436032

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with advanced AML that harbors IDH1 mutation

          -  Patients are relapsed from or refractory to at least 1 previous line of therapy

          -  Good kidney and liver function

          -  Male or female patients

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          -  Women must have a negative serum pregnancy test within 7 days prior to the first dose
             of study drug or be surgically or biologically sterile or postmenopausal

        Exclusion Criteria:

          -  Previously treated with any prior mIDH1 targeted therapy

          -  Extramedullary disease only

          -  History of clinically significant or active cardiac disease

          -  Active clinically significant infection

          -  Unresolved chronic toxicity of previous AML treatment

          -  Taking known strong cytochrome P450 (CYP) 2C8 inducers or inhibitors

          -  Pregnancy or breast-feeding
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) or RP2D of BAY1436032
Time Frame:Within first 4 weeks of first dose
Safety Issue:
Description:If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032

Secondary Outcome Measures

Measure:Objective efficacy response
Time Frame:Up to 12 weeks
Safety Issue:
Description:Response assessment for AML in this study will be based on the modified Cheson criteria. The following categories are used to capture the investigator's AML response evaluation: Complete remission (CR) Morphologic CR with CRh (morphologic CR with incomplete hematological recovery) and the response category CRp (morphologic CR with incomplete platelet recovery) Partial remission (PR) Response categories for morphologic leukemia-free state (MLFS), stable disease and progressive disease Progressive disease
Measure:Duration of response
Time Frame:Up to 12 weeks
Safety Issue:
Description:Efficacy data
Measure:Event-free survival (EFS)
Time Frame:Up to 12 weeks
Safety Issue:
Description:EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
Measure:Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
Time Frame:Up to 12 weeks
Safety Issue:
Description:Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY 1436032 administration in patients. Change from baseline and percent change from baseline will be calculated.
Measure:Cmax (maximum observed drug concentration in plasma after a single dose)
Time Frame:Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
Safety Issue:
Description:As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated.
Measure:AUC(0-8) (AUC from time 0 to 8 h after a single dose)
Time Frame:Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
Safety Issue:
Description:As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated.
Measure:AUC(0-12) (AUC from time 0 to 12 h after a single dose)
Time Frame:Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
Safety Issue:
Description:if feasible
Measure:Cmax,md (Cmax after multiple doses)
Time Frame:Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
Safety Issue:
Description:As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated.
Measure:AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
Time Frame:Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Safety Issue:
Description:As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients. PK parameters normalized for dose and / or dose and body weight will be calculated.
Measure:AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
Time Frame:Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Safety Issue:
Description:if feasible

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Bayer

Trial Keywords

  • Phase 1
  • mIDH1
  • IDH1 mutation
  • mIDH1 inhibitor

Last Updated

May 14, 2019