Acute Myeloid Leukemia
Conditions
Keywords
FLT3, FLT3-ITD, FLT-TKD, AML, FLT3 Wild-Type, MLL-R, NPM1, CYP3A4
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.
Interventions
DRUGBMF-500
Investigational Product
Sponsors
Biomea Fusion Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Accelerated Titration Design, Followed by Modified 3+3
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety and tolerability of BMF-500 by incidence of Treatment Emergent Adverse Events (TEAEs). | At the end of each 28 Day cycle for a maximum of 32 cycles | Assessed by the NCI CTCAE version 5.0. |
| Evaluate the safety and tolerability of BMF-500 by incidence of Serious Adverse Events (SAEs). | At the end of each 28 Day cycle for a maximum of 32 cycles | Assessed by the NCI CTCAE version 5.0. |
| Determine the recommended Phase 2 Dose (RP2D) of BMF-500. | At the end of 28 day Dose-Limiting Toxicities (DLT) observation Period | Safety, as determined by Dose-Limiting Toxicities (clinically significant Adverse Event) within each dose level assessed NCI CTCAE version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the pharmacokinetics of BMF-500. | At the end of each cycle (each cycle is 28 days in duration) for 7 cycles | Maximum plasma concentration (Cmax). |
| Evaluate the efficacy of BMF-500 | At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles | Composite Complete Remission (CRc). |
| Assess additional evidence of antitumor activity per investigator assessment as per corresponding response criteria. | At the end of each cycle (each cycle is 28 days in duration) for a maximum of 32 cycles | Duration of Response (DOR). |
Countries
United States
Outcome results
None listed