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

Leukemia, Myeloid, Acute Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03127735
• Other study ID #: 19036
• Secondary ID: 2016-004095-22
• Status: Completed
• Phase: Phase 1
• Start date: June 14, 2017
• Est. completion date: March 15, 2019

Study information

• Verified date: May 2019
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 15, 2019
• Est. primary completion date: December 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

Country	Name	City	State
Germany	Universitätsklinikum Charite zu Berlin	Berlin
Germany	Universitätsklinikum Hamburg Eppendorf (UKE)	Hamburg
Germany	Medizinische Hochschule Hannover (MHH)	Hannover	Niedersachsen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Universitätsklinikum Leipzig AöR	Leipzig	Sachsen
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Ohio State University	Columbus	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mount Sinai Medical Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Within first 4 weeks of first dose
Primary	Number of participants with Adverse Events as a Measure of	As a measure of safety and tolerability	Up to 12 weeks
Secondary	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	Up to 12 weeks
Secondary	Duration of response	Efficacy data	Up to 12 weeks
Secondary	Event-free survival (EFS)	EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.	Up to 12 weeks
Secondary	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.	Up to 12 weeks
Secondary	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.	Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
Secondary	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.	Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
Secondary	AUC(0-12) (AUC from time 0 to 12 h after a single dose)	if feasible	Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
Secondary	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.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
Secondary	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.	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Secondary	AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)	if feasible	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)