Brief Summary
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral FLT3 inhibitor, in adult patients with acute leukemia.
Brief Title
A Phase 1, Study of BMF-500 in Adults With Acute Leukemia
Detailed Description
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adult patients with acute myeloid leukemia (AML), who may or may not be on Antifungals.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-844-245-0490
Central Contact Email
clinicaltrials@biomeafusion.com
Central Contact Role
Contact
Central Contact Phone
1-844-245-0490
Central Contact Email
clinicaltrials@biomeafusion.com
Completion Date
Completion Date Type
Estimated
Conditions
Acute Myeloid Leukemia
Eligibility Criteria
Key Inclusion Criteria:
* Age ≥ 18 years.
* Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
* ECOG performance status of 0-2.
* Adequate liver and renal function
* Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
* Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
* Arm B: Participants must have received a necessary azole antifungal(s) that is a strong CYP3A4 inhibitor (excluding other strong CYP3A4 inhibitor\[s\]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.
* Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks (Cycle 1).
Key Exclusion Criteria:
* Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within 6 months prior to the first dose of the trial intervention.
* WBC count \>50,000/µL (uncontrollable with cytoreductive therapy).
* Women who are pregnant or lactating or plan to become pregnant.
* Age ≥ 18 years.
* Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
* ECOG performance status of 0-2.
* Adequate liver and renal function
* Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
* Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
* Arm B: Participants must have received a necessary azole antifungal(s) that is a strong CYP3A4 inhibitor (excluding other strong CYP3A4 inhibitor\[s\]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.
* Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks (Cycle 1).
Key Exclusion Criteria:
* Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within 6 months prior to the first dose of the trial intervention.
* WBC count \>50,000/µL (uncontrollable with cytoreductive therapy).
* Women who are pregnant or lactating or plan to become pregnant.
Inclusion Criteria
Inclusion Criteria:
* Age ≥ 18 years.
* Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
* ECOG performance status of 0-2.
* Adequate liver and renal function
* Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
* Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
* Arm B: Participants must have received a necessary azole antifungal(s) that is a strong CYP3A4 inhibitor (excluding other strong CYP3A4 inhibitor\[s\]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.
* Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks (Cycle 1).
* Age ≥ 18 years.
* Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML with documented FLT3 mutation, and/or Individuals with histologically or pathologically confirmed diagnosis of their malignancy with wild-type FLT3 (including those with MLL1-R and NPM1 mutations).
* ECOG performance status of 0-2.
* Adequate liver and renal function
* Adhere to the CYP3A4 inhibitor concomitant therapy use requirements, as follows:
* Arm A: Participants must not have received a moderate or strong CYP3A4 inhibitor for at least 7 days prior to enrollment and are not anticipated to require such agents in the near term (for at least 4 weeks).
* Arm B: Participants must have received a necessary azole antifungal(s) that is a strong CYP3A4 inhibitor (excluding other strong CYP3A4 inhibitor\[s\]) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks.
* Arm C: Participants must have received necessary azole antifungal(s) that are moderate CYP3A4 inhibitors (excluding other moderate CYP3A4 inhibitors) for at least 7 days prior to enrollment and be able to continue such azole antifungal(s) while on BMF-500 treatment for at least 4 weeks (Cycle 1).
Gender
All
Gender Based
false
Keywords
FLT3
FLT3-ITD
FLT-TKD
AML
FLT3 Wild-Type
MLL-R
NPM1
CYP3A4
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05918692
Org Class
Industry
Org Full Name
Biomea Fusion Inc.
Org Study Id
COVALENT-103
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study of BMF-500, an Oral Covalent FLT3 Inhibitor, in Adults With Acute Leukemia
Primary Outcomes
Outcome Description
Assessed by the NCI CTCAE version 5.0.
Outcome Measure
Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs).
Outcome Time Frame
At the end of each 28 Day cycle for a maximum of 32 cycles
Outcome Description
Assessed by the NCI CTCAE version 5.0.
Outcome Measure
Evaluate the safety and tolerability of BMF-500 by incidence of Serious Adverse Events (SAEs).
Outcome Time Frame
At the end of each 28 Day cycle for a maximum of 32 cycles
Outcome Description
Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0.
Outcome Measure
Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
Outcome Time Frame
At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Outcome Description
Efficacy within each dose level as determined by composite complete remission (CRc).
Outcome Measure
Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
Outcome Time Frame
At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Outcome Description
Pharmacovigilance (PK) at each dose level as determined by the maximum plasma concentration (Cmax).
Outcome Measure
Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
Outcome Time Frame
At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Outcome Description
Pharmacovigilance (PK) at each dose level as determined by area under the curve plasma concentration from time 0 to last quantifiable concentration (AUClast).
Outcome Measure
Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
Outcome Time Frame
At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Secondary Outcomes
Outcome Description
Maximum plasma concentration (Cmax).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for 7 cycles
Outcome Measure
Determine the pharmacokinetics of BMF-500.
Outcome Description
Area under the curve plasma concentration from time 0 to last quantifiable concentration (AUClast).
Outcome Time Frame
At the end of Cycle 1 and 2 (each cycle is 28 days in duration)
Outcome Measure
Determine the pharmacokinetics of BMF-500.
Outcome Description
Composite Complete Remission (CRc).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Outcome Measure
Evaluate the efficacy of BMF-500
Outcome Description
Duration of Response (DOR).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Outcome Measure
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
Outcome Description
Overall Reasons Rate (ORR).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Outcome Measure
Evaluate the efficacy of BMF-500
Outcome Description
Relapse free survival (RFS).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Outcome Measure
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
Outcome Description
Overall Survival (OS).
Outcome Time Frame
At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Outcome Measure
Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
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