A Phase 1, Study of BMF-500 in Adults With Acute Leukemia

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05918692
• Other study ID #: COVALENT-103
• Status: Recruiting
• Phase: Phase 1
• Start date: July 26, 2023
• Est. completion date: July 31, 2026

Study information

• Verified date: May 2024
• Source: Biomea Fusion Inc.
• Contact: Mona Vimal
• Phone: 1-844-245-0490
• Email: clinicaltrials[@]biomeafusion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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), acute lymphocytic leukemia (ALL) and Acute Mixed-Phenotype Leukemia (MPAL) who may or may not be on Antifungals.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: July 31, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Age = 18 years.

• Individuals with histologically or pathologically confirmed diagnosis of relapsed or refractory AML, ALL, or MPAL 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 moderate or strong CYP3A4 inhibitor (excluding other moderate or 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.

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• BMF-500
Investigational Product

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Montefiore Hospital - Moses Campus - BRANY - PPDs	Bronx	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Duchossois Center for Advanced Medicine (DCAM)	Chicago	Illinois
United States	Cleveland Clinic Hospital	Cleveland	Ohio
United States	Texas Oncology-PA USOR	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Virginia Cancer Specialists	Gainesville	Virginia
United States	East Carolina University	Greenville	North Carolina
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kentucky - Markey Cancer Center	Lexington	Kentucky
United States	UCLA Department of Medicine	Los Angeles	California
United States	Northwell Health Cancer Institute	New Hyde Park	New York
United States	University of Oklahoma - Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Davis	Sacramento	California
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biomea Fusion Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and tolerability of BMF-500 monotherapy by incidence of Treatment Emerging Adverse Events (TEAEs).	Assessed by the NCI CTCAE version 5.0.	At the end of each 28 Day cycle for a maximum of 32 cycles
Primary	Evaluate the safety and tolerability of BMF-500 monotherapy by incidence of Serious Adverse Events (SAEs).	Assessed by the NCI CTCAE version 5.0.	At the end of each 28 Day cycle for a maximum of 32 cycles
Primary	Determine the recommended Phase 2 Dose (RP2D) of BMF-500.	Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0.	At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Primary	Determine the recommended Phase 2 Dose (RP2D) of BMF-500.	Efficacy within each dose level as determined by composite complete remission (CRc).	At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Primary	Determine the recommended Phase 2 Dose (RP2D) of BMF-500.	Pharmacovigilance (PK) at each dose level as determined by the maximum plasma concentration (Cmax).	At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Primary	Determine the recommended Phase 2 Dose (RP2D) of BMF-500.	Pharmacovigilance (PK) at each dose level as determined by area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).	At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Secondary	Determine the pharmacokinetics of BMF-500.	Maximum plasma concentration (Cmax).	At the end of each cycle (each cycle is 28 days in duration) for 7 cycles
Secondary	Determine the pharmacokinetics of BMF-500.	Area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).	At the end of each cycle (each cycle is 28 days in duration) for 7 cycles
Secondary	Assess the effect of food on the PK exposure of BMF-500 in participants receiving BMF-500 (for escalation only).	Maximum plasma concentration (Cmax).	At the end of cycle 1 and 2 (each cycle is 28 days in duration)
Secondary	Assess the effect of food on the PK exposure of BMF-500 in participants receiving BMF-500 (for escalation only).	Area under the plasma concentration from time 0 to last quantifiable concentration (AUClast).	At the end of cycle 1 and 2 (each cycle is 28 days in duration)
Secondary	Evaluate the efficacy of BMF-500	Composite Complete Remission (CRc).	At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Secondary	Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.	Duration of Response (DOR).	At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Secondary	Evaluate the efficacy of BMF-500	Overall Reasons Rate (ORR).	At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Secondary	Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.	Relapse free survival (RFS).	At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Secondary	Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.	Overall Survival (OS).	At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles