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

July 1, 2025 updated by: Biomea Fusion Inc.

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 Leukemia (AL), Diffuse Large B-cell Lymphoma (DLBCL), Multiple Myeloma (MM), and Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 106 76
        • Evangelismos General Hospital of Athens
      • Athens, Greece, 115 28
        • Alexandra General Hospital of Athens
  • Italy
      • Ancona, Italy, 60126
        • AOU Ospedali Riuniti Ancona
      • Bergamo, Italy, 24128
        • ASST Papa Giovanni XXIII Hospital Bergamo
      • Milan, Italy, 20089
        • Instituto Clinico Humanitas
      • Milan, Italy, 20132
        • IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC
      • Milano, Italy, 435 - 20141
        • Istituto Europeo Di Oncologia
      • Perugia, Italy, 06132
        • Ospedale Santa Maria Della Misericordia
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Netherlands
      • Amsterdam, Netherlands, 1081HV
        • Amsterdam UMC
      • Groningen, Netherlands, 9700 RB
        • UMCG Groningen
      • Nijmegen, Netherlands, 6500 HB
        • Radboud University Medical Center
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus University Medical Center Rotterdam
  • Spain
      • Albacete, Spain, 02006
        • Hospital General de Albacete
      • Barcelona, Spain, 08036
        • Hospital Clínic de Barcelona
      • Barcelona, Spain, 08916
        • Institut Catala d'Oncologia
      • Cáceres, Spain, 10003
        • Hospital San Pedro de Alcantara
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28006
        • Hospital Universitario de La Princesa
      • Oviedo, Spain, 33011
        • Hospital Universitario Central de Asturias
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Hospital Universitario y Politécnico La Fe
  • United States
    • California
      • Irvine, California, United States, 92697
        • University of California, Irvine
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine
      • Los Angeles, California, United States, 90033
        • University of Southern California Norris Cancer Center
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center
      • Stanford, California, United States, 94305
        • Stanford Cancer Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Medical Center
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Blood & Marrow Transplant Group of GA (Northside Hospital)
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Md Anderson Cancer Center
    • Virginia
      • Gainesville, Virginia, United States, 20155
        • Virginia Cancer Specialists

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
  • 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.
Drug: BMF-219
BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.
Other Names:
  • Covalent Menin Inhibitor
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 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.
Drug: BMF-219
BMF-219 is orally administered in continuous 28 day cycles. Alternative BID dosage may be used.
Other Names:
  • Covalent Menin Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)
Time Frame: At the end of Cycle 1 (each Cycle is 28 Days in duration)
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), multiple myeloma (Cohort 3), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (Cohort 4).
At the end of Cycle 1 (each Cycle is 28 Days in duration)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the Safety treatment-emergent TEAEs and SAEs
Time Frame: 28 Days after last dose.
Evaluate the Safety of BMF-219 as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
28 Days after last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biomea Fusion Inc.

Investigators

  • Study Director: Steve Morris, MD, Biomea Fusion Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2022

Primary Completion (Actual)

February 13, 2025

Study Completion (Actual)

May 2, 2025

Study Registration Dates

First Submitted

November 30, 2021

First Submitted That Met QC Criteria

November 30, 2021

First Posted (Actual)

December 10, 2021

Study Record Updates

Last Update Posted (Actual)

July 3, 2025

Last Update Submitted That Met QC Criteria

July 1, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COVALENT-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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