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Clinical Trial 21761

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT05153330

Phase: Phase I
Principal Investigator: Lancet, Jeffrey

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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

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

Therapy (NOS)

Medications

BMF-219 ()

Inclusion Criteria

Inclusion Criteria:

  • Age 18 or older
  • Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood and who have failed or are ineligible for any approved standard of care therapies, including HSCT.
  • Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization by patient or legal guardian after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures including serial bone marrow and peripheral blood sampling.
  • ECOG performance status of 0-2
  • Adequate liver and renal function as defined in protocol
  • Hydroxyurea will be allowed prior to enrollment and after the start of BMF-219 to control and maintain peripheral white blood cell (WBC) counts ≤ 25,000/μL. Subjects can continue on hydroxyurea through Cycle 1 Day 28 or until first disease assessment. After which, patients should be titrated off of therapy.
  • 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 120 days after discontinuing study treatment. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
  • Any prior treatment-related toxicities resolved to ≤Grade 2 prior to enrollment
  • Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
  • Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion (DLI) without conditioning.
  • Immunotherapy: At least 21 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T-cell therapy.
  • Myelosuppressive Chemotherapy: At least 14 days since the completion of cytotoxic/myelosuppressive therapy.
  • Biologics: At least 7 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent.
  • Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy

  • Exclusion Criteria

    Exclusion criteria:

  • Diagnosis of acute promyelocytic leukemia.
  • Diagnosis of chronic leukemia in blast crisis.
  • Isolated extramedullary relapse.
  • WBC count > 25,000/ µL (uncontrollable with cytoreductive therapy).
  • Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable, however
  • Patients who have undergone HSCT and have not had adequate hematologic recovery (i.e., ANC >500 and platelet count > 50K).
  • Patients who received chemotherapy, immunotherapy, or radiotherapy or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indication(s) and in the context of a research investigation) > Prior menin inhibitor therapy.
  • 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).
  • An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.
  • Significant cardiovascular disease
  • Mean QTcF or QTcB of > 470 millisecond (ms) on triplicate ECGs performed within 5 minutes of each other (as a guide to known drugs associated with QTc prolongation, please refer to the following Credible Meds web page for a list of drugs that prolong QT and/or cause Torsades de Pointes
  • Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patient should be recovered.
  • Gastrointestinal Disease: (a) Chronic diarrhea or other gastrointestinal issue that might affect oral drug absorption or ingestion (e.g., short-gut syndrome, gastroparesis, etc.) (b) Cirrhosis with a Child-Pugh score of B or C.
  • Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute GVHD of any severity or chronic GVHD other than disease limited to skin that is adequately controlled with topical steroids alone within 4 weeks of enrollment. All transplant patients must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. The use of topical steroids for cutaneous GVHD is allowed and stable systemic steroid doses less than or equal to 10 mg of prednisone daily is permitted with Medical Monitor approval.
  • Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe
  • Any underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or AEs.
  • Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test prior to starting study treatment.
  • Known alcohol or drug abuse

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