Clinical trial NCT03127735: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Keywords: Phase 1
mIDH1
IDH1 mutation
mIDH1 inhibitor
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2017-04-25
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Maximum tolerated dose (MTD) or RP2D of BAY1436032
timeFrame: Within first 4 weeks of first dose
measure: Number of participants with Adverse Events as a Measure of
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Objective efficacy response
timeFrame: Up to 12 weeks
measure: Duration of response
timeFrame: Up to 12 weeks
measure: Event-free survival (EFS)
timeFrame: Up to 12 weeks
measure: Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
timeFrame: Up to 12 weeks
measure: Cmax (maximum observed drug concentration in plasma after a single dose)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
measure: AUC(0-8) (AUC from time 0 to 8 h after a single dose)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
measure: AUC(0-12) (AUC from time 0 to 12 h after a single dose)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
measure: Cmax,md (Cmax after multiple doses)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
measure: AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
measure: AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
state: Niedersachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
state: Sachsen
city: Berlin
country: Germany
facility: Universitätsklinikum Charite zu Berlin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf (UKE)
Study officials:
References: