check_circleStudy Completed

Leukemia, Myeloid, Acute

Bayer Identifier:

19036

ClinicalTrials.gov Identifier:

NCT03127735

EudraCT Number:

2016-004095-22

EU CT Number:

Not Available
BAY1436032 in patients with mutant IDH1(mIDH1) advanced acute myeloid leukemia (AML)

Trial 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)

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
27
Trial Dates
June 2017 - March 2019
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY1436032
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum HeidelbergHeidelberg, 69120, Germany
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
Ohio State UniversityColumbus, 43210, United States
Withdrawn
University of Florida-GainesvilleGainesville, 32608, United States
Completed
Universitätsklinikum Leipzig AöRLeipzig, Germany
Completed
Roswell Park Comprehensive Cancer CenterBuffalo, 14263-0001, United States
Completed
Montefiore Medical CenterBronx, 10467-2490, United States
Completed
Wake Forest Baptist HealthWinston-Salem, 27157, United States
Completed
University of PennsylvaniaPhiladelphia, 19104, United States
Withdrawn
Northwestern Memorial HospitalChicago, 60611-2908, United States
Completed
Mount Sinai Medical CenterNew York, 10029, United States
Completed
Medizinische Hochschule Hannover (MHH)Hannover, 30625, Germany
Completed
Universitätsklinikum Hamburg Eppendorf (UKE)Hamburg, 20246, Germany
Completed
Universitätsklinikum Charite zu BerlinBerlin, 12200, Germany
Completed
Thomas Jefferson UniversityPhiladelphia, 19107, United States
Withdrawn
University of ChicagoChicago, 60637, United States
Withdrawn
Klinikum rechts der IsarMünchen, 81675, Germany
Withdrawn
University of Southern California Keck School of MedicineLos Angeles, 90033-9172, United States
Withdrawn
Northside Hospital - AtlantaAtlanta, 30342, United States
Withdrawn
Universitätsklinikum EssenEssen, 45122, Germany

Primary Outcome

  • Maximum tolerated dose (MTD) or RP2D of BAY1436032
    If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
    date_rangeTime Frame:
    Within first 4 weeks of first dose
    enhanced_encryption
    Safety Issue:
    Yes
  • Number of participants with Adverse Events as a Measure of
    As a measure of safety and tolerability
    date_rangeTime Frame:
    Up to 12 weeks
    enhanced_encryption
    Safety Issue:
    Yes

Secondary Outcome

  • Objective efficacy response
    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
    date_rangeTime Frame:
    Up to 12 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Duration of response
    Efficacy data
    date_rangeTime Frame:
    Up to 12 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Event-free survival (EFS)
    EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
    date_rangeTime Frame:
    Up to 12 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
    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.
    date_rangeTime Frame:
    Up to 12 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Cmax (maximum observed drug concentration in plasma after a single dose)
    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.
    date_rangeTime 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)
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-8) (AUC from time 0 to 8 h after a single dose)
    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.
    date_rangeTime Frame:
    Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) (AUC from time 0 to 12 h after a single dose)
    if feasible
    date_rangeTime Frame:
    Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
    enhanced_encryption
    Safety Issue:
    No
  • Cmax,md (Cmax after multiple doses)
    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.
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
    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.
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
    if feasible
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
    enhanced_encryption
    Safety Issue:
    No

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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