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

NCT03127735 | Completed Phase 1 FDA Drug

• 2 other identifiers: 190362016-004095-22
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 13

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)

Conditions

Leukemia, Myeloid, Acute

Keywords

Phase 1; mIDH1; IDH1 mutation; mIDH1 inhibitor

Outcome Measures

Primary Outcomes (2)

• 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

• Number of participants with Adverse Events as a Measure of

  As a measure of safety and tolerability

  Up to 12 weeks

Secondary Outcomes (10)

• Objective efficacy response

  Up to 12 weeks

• Duration of response

  Up to 12 weeks

• Event-free survival (EFS)

  Up to 12 weeks

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

  Up to 12 weeks

• 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)

Study Arms (1)

BAY1436032

EXPERIMENTAL

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

Interventions

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.

BAY1436032

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (13)

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263-0001, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Medizinische Hochschule Hannover (MHH)

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsklinikum Leipzig AöR

Leipzig, Saxony, Germany

Location

Universitätsklinikum Charite zu Berlin

Berlin, 12200, Germany

Location

Universitätsklinikum Hamburg Eppendorf (UKE)

Hamburg, 20246, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

BAY 1436032

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 25, 2017
• Study Start: June 14, 2017
• Primary Completion: December 6, 2018
• Study Completion: March 15, 2019
• Last Updated: May 14, 2019

Record last verified: 2019-05

Locations

DE (5); US (8)