Study of BMF-219, in Adult Patients With Acute Leukemia, Diffuse Large B-Cell Lymphoma and Multiple Myeloma
Study Details
Study Description
Brief Summary
A Phase1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral irreversible menin inhibitor, in adult patients with acute leukemia, diffuse large B-cell lymphoma, and multiple myeloma
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF 219, an oral irreversible menin inhibitor, in adult patients with acute leukemia (AL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM)
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Dose Escalation Phase Experimental: ARM A: Study participants who are not receiving a moderate or strong CYP3A4 inhibitor. Dose Escalation Phase: Cohort 1: participants with acute leukemia Cohort 2: participants with diffuse large B-cell lymphoma Cohort 3: participants with multiple myeloma Participants will receive 100 mg BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose) Dose Expansion Phase: Cohorts 1, 2, and 3 will receive BMF-219 at the OPD/RP2D to further assess the safety/efficacy of the investigational drug. |
Drug: BMF-219
BMF-219 is orally administered once daily in continuous 28 day cycles.
Other Names:
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Experimental: Dose Expansion Experimental: ARM B: Study participants who are receiving a moderate or strong CYP3A4 inhibitor. Dose Escalation Phase: • Cohort 1: participants with acute leukemia will receive 25 mg BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose). Dose Expansion Phase: Cohort 1 will receive BMF-219 at the OBD/RP2D to further assess the safety and efficacy of the investigational drug. |
Drug: BMF-219
BMF-219 is orally administered once daily in continuous 28 day cycles.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2 and 3) [28 days]
Determine Optimal Biologic Dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 monotherapy in subjects with refractory or relapsed (R/R) acute leukemia (Cohort 1), diffuse large B-cell lymphoma (Cohort 2), and multiple myeloma (Cohort 3)
Secondary Outcome Measures
- Evaluate the Safety by treatment-emergent TEAEs and SAEs [32 cycles]
Evaluate the Safety by treatment-emergent TEAEs and SAEs Evaluate safety of BMF-219 as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/or measurable R/R disease, as follows:
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Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood
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Cohort 2 only: Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously indolent lymphoma (e.g., follicular lymphoma) with documented clinical or radiological evidence of progressive or persistent disease. At study entry, subjects must have measurable disease as per the revised criteria for response assessment of lymphoma.
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Cohort 3 only: Measurable MM based on IMWG (International Myeloma Working Group) guidelines
Patients must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations:
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Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation)
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Cohort 2 only: Must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL (i.e., transformed from a previously diagnosed indolent lymphoma [e.g., follicular lymphoma])
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Cohort 3 only: Must have received at least 3 but no more than 6 prior anti-MM regimens including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory drug (IMiD) (e.g., lenalidomide or pomalidomide) therapy.
Exclusion Criteria:
Subjects who meet any of the following criteria will not be enrolled in the study (all cohorts, unless otherwise indicated):
- Certain disease subtypes or occurrences, as follows:
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Cohort 1: acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis, isolated extramedullary relapse (iEMR).
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Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL)
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Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis
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White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy)
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Known central nervous involvement, as follows:
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Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable
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Cohort 2: Active CNS lymphoma or meningeal involvement
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Prior menin inhibitor therapy
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Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen
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Subjects with a pre-existing disorder predisposing them to a serious or life-threatening infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to acute leukemia, DLBCL, or MM)
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An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | UCLA Department of Medicine | Los Angeles | California | United States | 90095 |
2 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
3 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
4 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45219 |
5 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
6 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
7 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Biomea Fusion Inc.
Investigators
- Study Director: Alex Cacovean, MD, Biomea Fusion Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BF-MNN-101