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

Phase 1

Completed

• Conditions: Leukemia, Myeloid, Acute
• Interventions: Drug: BAY1436032

• Registration Number: NCT03127735
• Lead Sponsor: 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)

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-04-06
• Study First Submitted QC: 2017-04-20
• Study First Posted: 2017-04-25
• Study Start: 2017-06-14
• Primary Completion: 2018-12-06
• Study Completion: 2019-03-15
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-13
• Last Update Posted: 2019-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BAY1436032	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.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) or RP2D of BAY1436032	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
Number of participants with Adverse Events as a Measure of	Up to 12 weeks	As a measure of safety and tolerability

Secondary Outcome Measures

Name	Time	Method
Duration of response	Up to 12 weeks	Efficacy data
AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)	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.
Event-free survival (EFS)	Up to 12 weeks	EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
Objective efficacy response	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
Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline	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.
Cmax (maximum observed drug concentration in plasma after a single dose)	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.
AUC(0-8) (AUC from time 0 to 8 h after a single dose)	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.
AUC(0-12) (AUC from time 0 to 12 h after a single dose)	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
Cmax,md (Cmax after multiple doses)	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.
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)	if feasible

Trial Locations

Locations (13)

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Baden-Württemberg, Germany

Medizinische Hochschule Hannover (MHH); 🇩🇪 Hannover, Niedersachsen, Germany

Universitätsklinikum Leipzig AöR; 🇩🇪 Leipzig, Sachsen, Germany

Universitätsklinikum Charite zu Berlin; 🇩🇪 Berlin, Germany

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

Wake Forest Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Universitätsklinikum Hamburg Eppendorf (UKE); 🇩🇪 Hamburg, Germany

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States