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Trial record 1 of 1 for:    covalent-101
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Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL

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ClinicalTrials.gov Identifier: NCT05153330
Recruitment Status : Recruiting
First Posted : December 10, 2021
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
Biomea Fusion Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
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 Drug: BMF-219 Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 177 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The first-in-human (FIH) study is a dose-escalation/dose-expansion study of BMF-219. During the dose-escalation phase of the study, the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 will be determined. Subjects in Cohort 1 (acute leukemia) are assigned to one of two parallel arms; ARM A (subjects not receiving CYP3A4 inhibitors) and ARM B (subjects receiving CYP3A4 inhibitors); Subjects in Cohort 2 (DLBCL), Cohort 3 (multiple myeloma), and Cohort 4 (chronic lymphocytic leukemia/ small lymphocytic lymphoma) are assigned to a single arm (ARM A).The dose-expansion phase will obtain further safety, as well as efficacy data for BMF-219 when dosed at the OBD and RP2D.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : January 24, 2022
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Covalent Menin Inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Evaluate the Safety treatment-emergent TEAEs and SAEs [ Time Frame: At the end of Cycle 1 (each Cycle is 28 Days in duration) ]
    Evaluate the Safety of BMF-219 as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 1 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05153330


Contacts
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Contact: Mona Vimal 1-844-245-0490 clinicaltrials@biomeafusion.com
Contact: Clarissa Mandap 1-844-245-0490 clinicaltrials@biomeafusion.com

Locations
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Sponsors and Collaborators
Biomea Fusion Inc.
Investigators
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Study Director: Alex Cacovean, MD Biomea Fusion Inc.
More Information
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Responsible Party: Biomea Fusion Inc.
ClinicalTrials.gov Identifier: NCT05153330    
Other Study ID Numbers: COVALENT-101
First Posted: December 10, 2021    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes