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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03127735
Recruitment Status : Completed
First Posted : April 25, 2017
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: BAY1436032 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 14, 2017
Actual Primary Completion Date : December 6, 2018
Actual Study Completion Date : March 15, 2019


Arm Intervention/treatment
Experimental: BAY1436032

Dose 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.

Drug: BAY1436032

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 Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127735


Locations
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United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States, 14263-0001
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Germany
Universitätsklinikum Heidelberg
Heidelberg, Baden-Württemberg, Germany, 69120
Medizinische Hochschule Hannover (MHH)
Hannover, Niedersachsen, Germany, 30625
Universitätsklinikum Leipzig AöR
Leipzig, Sachsen, Germany
Universitätsklinikum Charite zu Berlin
Berlin, Germany, 12200
Universitätsklinikum Hamburg Eppendorf (UKE)
Hamburg, Germany, 20246
Sponsors and Collaborators
Bayer
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03127735    
Other Study ID Numbers: 19036
2016-004095-22 ( EudraCT Number )
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Phase 1
mIDH1
IDH1 mutation
mIDH1 inhibitor
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms