Clinical Trial 21761

• Overview

  Study Title:

  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 Including Those with an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (Covalent-101)

  Summary:

  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)

  Objective:

  1. Determine the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 monotherapy; 2. Evaluate the safety as expressed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs); 3. Determine maximum observed plasma concentration (Cmax), time to reach maximum observed concentration (Tmax), and area under plasma-concentration time curve from time 0 to time of last quantifiable concentration (AUC0-last) of BMF-219; 4. Evaluate the efficacy of BMF-219 as measured by complete remission rate (CRR) per Investigator assessment; 5. Assess additional evidence of antitumor activity.

• Treatments

  Therapies:

  Bone Marrow Transplant; Therapy (NOS)

  Medications:

  BMF-219 ()

• Inclusion Criteria

  Inclusion Criteria:
  • Histologically or pathologically confirmed diagnosis of their malignancy and/or measurable R/R disease, as follows:
  • Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood. Specific mutational statuses may be required for allocation to a specific cohort.
  • 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.
  • Cohort 3 only: Measurable MM based on requirements listed per protocol
  • Patients must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations:
  • Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation)
  • Cohort 2 only: Must have received at least 2 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])
  • Cohort 3 only: Must have received at least 3 prior anti-MM regimens including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory drug (IMiD) (e.g., lenalidomide or pomalidomide) therapy.
  • Other criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Certain disease subtypes or occurrences, as follows:
  • Cohort 1: acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis, isolated extramedullary relapse (iEMR).
  • Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL)
  • Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis
  • White Blood Count (WBC) > 50,000 (uncontrollable with cytoreductive therapy)
  • Known central nervous involvement, as follows:
  • Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable
  • Cohort 2: Active CNS lymphoma or meningeal involvement
  • Prior menin inhibitor therapy (except for patients in Cohort 1)
  • Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen
  • Patients 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)
  • An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection
  • Other criteria may apply

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