Clinical trial NCT05153330: Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: Biomea Fusion Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)
timeFrame: At the end of Cycle 1 (each Cycle is 28 Days in duration)
Secondary outcomes:
measure: Evaluate the Safety treatment-emergent TEAEs and SAEs
timeFrame: At the end of Cycle 1 (each Cycle is 28 Days in duration)
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Blood & Marrow Transplant Group of GA (Northside Hospital)
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti Ancona
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII Hospital Bergamo
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Instituto Clinico Humanitas
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele, Programma di Ricerca Strategica su LLC
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Groningen
country: Netherlands
facility: UMCG Groningen
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Albacete
country: Spain
facility: Hospital General de Albacete
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Biomea Fusion Inc.
name: Steve Morris, MD
role: STUDY_DIRECTOR
References: