Clinical trial NCT05918692: A Phase 1, Study of BMF-500 in Adults With Acute Leukemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: FLT3
FLT3-ITD
FLT-TKD
AML
FLT3 Wild-Type
MLL-R
NPM1
CYP3A4
Lead sponsor: Biomea Fusion Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Accelerated Titration Design, Followed by Modified 3+3
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs).
timeFrame: At the end of each 28 Day cycle for a maximum of 32 cycles
measure: Evaluate the safety and tolerability of BMF-500 by incidence of Serious Adverse Events (SAEs).
timeFrame: At the end of each 28 Day cycle for a maximum of 32 cycles
measure: Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
timeFrame: At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
measure: Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
timeFrame: At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
measure: Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
timeFrame: At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
measure: Determine the recommended Phase 2 Dose (RP2D) of BMF-500.
timeFrame: At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period
Secondary outcomes:
measure: Determine the pharmacokinetics of BMF-500.
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for 7 cycles
measure: Determine the pharmacokinetics of BMF-500.
timeFrame: At the end of Cycle 1 and 2 (each cycle is 28 days in duration)
measure: Evaluate the efficacy of BMF-500
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
measure: Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
measure: Evaluate the efficacy of BMF-500
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
measure: Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
measure: Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria.
timeFrame: At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Duchossois Center for Advanced Medicine (DCAM)
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky - Markey Cancer Center
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Hospital - Moses Campus - BRANY - PPDs
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma - Stephenson Cancer Center
state: Oklahoma
city: Dallas
country: United States
facility: Texas Oncology-PA USOR
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
References: