Leukemia, Myeloid, Acute
Conditions
Keywords
Phase 1, mIDH1, IDH1 mutation, mIDH1 inhibitor
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)
Interventions
DRUGBAY1436032
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.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events as a Measure of | Up to 12 weeks | As a measure of safety and tolerability |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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(0-8)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. |
| 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 |
| 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 |
| Duration of response | Up to 12 weeks | Efficacy data |
Countries
Germany, United States
Outcome results
None listed