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

Primary Purpose

Leukemia, Myeloid, Acute

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BAY1436032
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Phase 1, mIDH1, IDH1 mutation, mIDH1 inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Montefiore Medical Center
  • Roswell Park Comprehensive Cancer Center
  • Mount Sinai Medical Center
  • Wake Forest Baptist Health
  • Ohio State University
  • University of Pennsylvania
  • Thomas Jefferson University
  • University of Texas MD Anderson Cancer Center
  • Universitätsklinikum Heidelberg
  • Medizinische Hochschule Hannover (MHH)
  • Universitätsklinikum Leipzig AöR
  • Universitätsklinikum Charite zu Berlin
  • Universitätsklinikum Hamburg Eppendorf (UKE)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BAY1436032

Arm Description

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.

Outcomes

Primary Outcome Measures

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
Number of participants with Adverse Events as a Measure of
As a measure of safety and tolerability

Secondary Outcome Measures

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
Duration of response
Efficacy data
Event-free survival (EFS)
EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
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.
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.
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.
AUC(0-12) (AUC from time 0 to 12 h after a single dose)
if feasible
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.
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.
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
if feasible

Full Information

First Posted
April 6, 2017
Last Updated
May 13, 2019
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT03127735
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
June 14, 2017 (Actual)
Primary Completion Date
December 6, 2018 (Actual)
Study Completion Date
March 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute
Keywords
Phase 1, mIDH1, IDH1 mutation, mIDH1 inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BAY1436032
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BAY1436032
Intervention Description
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 Measure Information:
Title
Maximum tolerated dose (MTD) or RP2D of BAY1436032
Description
If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
Time Frame
Within first 4 weeks of first dose
Title
Number of participants with Adverse Events as a Measure of
Description
As a measure of safety and tolerability
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Objective efficacy response
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
Time Frame
Up to 12 weeks
Title
Duration of response
Description
Efficacy data
Time Frame
Up to 12 weeks
Title
Event-free survival (EFS)
Description
EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
Time Frame
Up to 12 weeks
Title
Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
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.
Time Frame
Up to 12 weeks
Title
Cmax (maximum observed drug concentration in plasma after a single dose)
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.
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)
Title
AUC(0-8) (AUC from time 0 to 8 h after a single dose)
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.
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)
Title
AUC(0-12) (AUC from time 0 to 12 h after a single dose)
Description
if feasible
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)
Title
Cmax,md (Cmax after multiple doses)
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.
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)
Title
AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
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.
Time Frame
Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Title
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
Description
if feasible
Time Frame
Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Medizinische Hochschule Hannover (MHH)
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Leipzig AöR
City
Leipzig
State/Province
Sachsen
Country
Germany
Facility Name
Universitätsklinikum Charite zu Berlin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Universitätsklinikum Hamburg Eppendorf (UKE)
City
Hamburg
ZIP/Postal Code
20246
Country
Germany

12. IPD Sharing Statement

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

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