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)
Brief Title
BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Leukemia, Myeloid, Acute
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Phase 1
mIDH1
IDH1 mutation
mIDH1 inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03127735
Org Class
Industry
Org Full Name
Bayer
Org Study Id
19036
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
Outcome Measure
Maximum tolerated dose (MTD) or RP2D of BAY1436032
Outcome Time Frame
Within first 4 weeks of first dose
Outcome Description
As a measure of safety and tolerability
Outcome Measure
Number of participants with Adverse Events as a Measure of
Outcome Time Frame
Up to 12 weeks
Secondary Ids
Secondary Id
2016-004095-22
Secondary Outcomes
Outcome Description
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
* 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
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Objective efficacy response
Outcome Description
Efficacy data
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Duration of response
Outcome Description
EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Event-free survival (EFS)
Outcome Description
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.
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
Outcome Description
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.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Outcome Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
Outcome Measure
Cmax (maximum observed drug concentration in plasma after a single dose)
Outcome Description
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.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Outcome Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
Outcome Measure
AUC(0-8) (AUC from time 0 to 8 h after a single dose)
Outcome Description
if feasible
Outcome Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
Outcome Measure
AUC(0-12) (AUC from time 0 to 12 h after a single dose)
Outcome Description
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.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Outcome Time Frame
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
Outcome Measure
Cmax,md (Cmax after multiple doses)
Outcome Description
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.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Outcome Time Frame
Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Outcome Measure
AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
Outcome Description
if feasible
Outcome Time Frame
Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Outcome Measure
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
BAY 1436032