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Completed

NCT Number: NCT03127735

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

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)

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Key information

Conditions

Leukemia, Myeloid, Acute Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Universitätsklinikum Heidelberg, Heidelberg, Baden-Wurttemberg, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BAY1436032

Drug

BAY1436032 administered continuously as a single agent dosed twice a day orally on Days 1 to 28 of a 28-day cycle.

Patients may continue treatment with BAY1436032 until disease progression, development of other unacceptable toxicity or Investigator discretion.

Primary outcomes

  1. Maximum tolerated dose (MTD) or RP2D of BAY1436032

    Time frame: Within first 4 weeks of first dose

    If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032

  2. Number of participants with Adverse Events as a Measure of

    Time frame: Up to 12 weeks

    As a measure of safety and tolerability

Secondary outcomes

  1. Objective efficacy response

    Time frame: Up to 12 weeks

    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

  2. Duration of response

    Time frame: Up to 12 weeks

    Efficacy data

  3. Event-free survival (EFS)

    Time frame: Up to 12 weeks

    EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.

  4. Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline

    Time frame: Up to 12 weeks

    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.

  5. 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)

    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.

  6. 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)

    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.

  7. 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)

    if feasible

  8. 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)

    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.

  9. 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)

    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.

  10. 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)

    if feasible

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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)

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Apr 25, 2017
Registry last updated
May 14, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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