Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL

NCT ID: NCT05153330

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2025-05-02

Brief Summary

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with AML, ALL (with KMT2A/ MLL1r, NPM1 mutations), DLBCL, MM, and CLL/SLL.

Detailed Description

A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) with mixed lineage leukemia 1-rearranged (KMT2A/ MLL1r), nucleophosmin 1 (NPM1), diffuse large b-cell lymphoma (DLBCL), multiple myeloma (MM), and chronic lymphocytic lymphoma (CLL)/ small lymphocytic lymphoma (SLL).

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Mixed-Phenotype Leukemia; Cancer; Refractory; Progression; Diffuse Large B Cell Lymphoma; Multiple Myeloma; Lymphoma; Lymphoma, Non-Hodgkin; Myeloma, Plasma-Cell; Myelomatosis; Plasma Cell Myeloma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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
• Cohort 4: Participants with chronic lymphocytic leukemia/ small lymphocytic lymphoma

Participants will receive escalating dose BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose).

Dose Expansion Phase:

Cohorts 1, 2, 3, and 4 will receive BMF-219 at the OBD/ RP2D to further assess the safety/ efficacy of the investigational drug.

Group Type: EXPERIMENTAL

BMF-219

Intervention Type: DRUG

BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.

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 escalating dose BMF-219 orally 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.

Group Type: EXPERIMENTAL

BMF-219

Intervention Type: DRUG

BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.

Interventions

BMF-219

BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.

Intervention Type: DRUG

Other Intervention Names

Covalent Menin Inhibitor

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years.
• All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/ or measurable R/ R disease, as follows:

1. Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood.

2. 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.

3. Cohort 3 only: Measurable MM.

4. Cohort 4 only: Previously treated subjects with active CLL/SLL with meeting at least 1 of the iwCLL 2018 criteria for requiring treatment.

• Subjects must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations:

1. Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation).

2. Cohort 2 only: Must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL.

3. Cohort 3 only: Must have received at least 3 anti-MM regimens including proteasome inhibitor.

4. Cohort 4 only: Must have received at least 2 prior systemic treatment regimens.

• ECOG performance status of 0-2 and an estimated expected life expectancy of > 3 months in the opinion of the Investigator.
• Adequate organ function.
• Both men and women of childbearing potential or their partners must use adequate birth control measures during the course of the trial and for at least 90 days after discontinuing study treatment.

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:

1. Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis.

2. Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL).

3. Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis.

4. Cohort 4: Known or suspected history of Richter's transformation.

• White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy) (Cohort 1 only).
• Known central nervous involvement, as follows:

1. Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable.

2. Cohort 2: Active CNS lymphoma or meningeal involvement.

3. Cohort 3: Active CNS MM.

4. Cohort 4: Active CNS leukemia.

• Prior menin inhibitor therapy.
• Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
• Subjects with a pre-existing disorder predisposing them to a serious or life-threatening infection.
• An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biomea Fusion Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Morris, MD

Role: STUDY_DIRECTOR

Biomea Fusion Inc.

Locations

University of California, Irvine

Irvine, California, United States

University of Southern California Norris Cancer Center

Los Angeles, California, United States

UCLA Department of Medicine

Los Angeles, California, United States

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Stanford Cancer Center

Stanford, California, United States

Mayo Clinic

Jacksonville, Florida, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Blood & Marrow Transplant Group of GA (Northside Hospital)

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Henry Ford Hospital

Detroit, Michigan, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Gainesville, Virginia, United States

Evangelismos General Hospital of Athens

Athens, , Greece

Alexandra General Hospital of Athens

Athens, , Greece

AOU Ospedali Riuniti Ancona

Ancona, , Italy

ASST Papa Giovanni XXIII Hospital Bergamo

Bergamo, , Italy

Instituto Clinico Humanitas

Milan, , Italy

IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Ospedale Santa Maria della Misericordia

Perugia, , Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Amsterdam UMC

Amsterdam, , Netherlands

UMCG Groningen

Groningen, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

Hospital General de Albacete

Albacete, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Institut Catala d'Oncologia

Barcelona, , Spain

Hospital San Pedro de Alcántara

Cáceres, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Countries

United States; Greece; Italy; Netherlands; Spain

Other Identifiers

COVALENT-101

Identifier Type: -

Identifier Source: org_study_id