A Study of Revumenib in Combination With Chemotherapy in Participants With R/R Acute Leukemia

NCT ID: NCT05326516

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-09
• Study Completion Date: 2024-07-29

Brief Summary

The purpose of this study is to determine the safety and tolerability of revumenib when given in combination with 2 different chemotherapy regimens in participants with relapsed/refractory acute leukemias harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.

Conditions

Relapsed/Refractory Leukemias; Acute Lymphoblastic Leukemia; Acute Lymphocytic Leukemia; Mixed Phenotype Acute Leukemia; Acute Myeloid Leukemia; Acute Undifferentiated Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Revumenib and Chemotherapy Regimen 1

Participants with acute lymphoblastic leukemia/mixed phenotype acute leukemia (ALL/MPAL) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 1.

Group Type: EXPERIMENTAL

Revumenib

Intervention Type: DRUG

Participants will receive revumenib until meeting criteria for discontinuation.

Chemotherapy Regimen 1

Intervention Type: DRUG

Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase/calaspargase pegol-mknL, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide.

Revumenib and Chemotherapy Regimen 2

Participants with ALL/MPAL or acute myeloid leukemia (AML) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 2.

Group Type: EXPERIMENTAL

Revumenib

Intervention Type: DRUG

Participants will receive revumenib until meeting criteria for discontinuation.

Chemotherapy Regimen 2

Intervention Type: DRUG

Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine.

Interventions

Revumenib

Participants will receive revumenib until meeting criteria for discontinuation.

Intervention Type: DRUG

Chemotherapy Regimen 1

Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase/calaspargase pegol-mknL, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide.

Intervention Type: DRUG

Chemotherapy Regimen 2

Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine.

Intervention Type: DRUG

Other Intervention Names

SNDX-5613

Eligibility Criteria

Inclusion Criteria

• Participants must have documented relapsed or refractory (R/R) AML, ALL, or acute leukemias of ambiguous lineage (ALAL) including MPAL and acute undifferentiated leukemia (AUL) harboring KMT2A rearrangement, KMT2A amplification, NPM1c, or NUP98r.
• White blood count must be <25,000/microliter prior to the first dose of revumenib. Participants may receive cytoreduction per protocol prior to beginning revumenib.
• Eastern Cooperative Oncology Group performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and <18 years); Lansky Performance Score of ≥50 (if aged <16 years).
• Adequate liver, kidney, and cardiac function
• Participant must be taking 1 of the following medications for antifungal prophylaxis: itraconazole, ketoconazole, posaconazole, or voriconazole.
• A female of childbearing potential must agree to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.

• A male of childbearing potential must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.

Exclusion Criteria

• Any unresolved ≥Grade 2 reversible toxicity from previous anticancer therapy except alopecia or Grade 2 neuropathy
• Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have discontinued all systemic immunosuppressive therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
• 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 (for example, 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. For participants with therapy-related leukemia, primary disease must be in remission for 1-year following completion of therapy.
• If the participant is known to be human immunodeficiency virus (HIV)-positive, the participant must have undetectable HIV viral load within the previous 6 months.
• Hepatitis B
• Hepatitis C
• Cardiac Disease:

• Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
• QTcF interval >450 milliseconds
• Any gastrointestinal (GI) issue of the upper GI tract that might affect oral drug absorption or ingestion (for example, gastric bypass, gastroparesis).
• Cirrhosis with a Child-Pugh score of B or C
• Down Syndrome
• Genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.
• Participation in another therapeutic interventional clinical study within 28 days of starting revumenib.
• Radiation Therapy: within 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or within 14 days from local palliative radiation therapy (small port).
• Stem Cell Infusion or Donor Lymphocyte Infusion: within 60 days from hematopoietic stem cell transplantation and within 28 days from donor lymphocyte infusion without conditioning.
• Biologics (for example, monoclonal antibody therapy, bispecific antibodies, and antibody-drug conjugates): within 28 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent.
• Immunotherapy: within 42 days since tumor vaccines and checkpoint inhibitors, and within 21 days since receipt of chimeric antigen receptor therapy or other modified T-cell therapy.
• Hematopoietic Growth Factors: within 7 days since the completion of therapy with short-acting hematopoietic growth factors and within 14 days with long-acting growth factors.

• Minimum Eligible Age: 30 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syndax Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicole McNeer, MD, PhD

Role: STUDY_DIRECTOR

Syndax Pharmaceuticals

Locations

University of California, San Francisco (UCSF) Benioff Children's Hospital

San Francisco, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

David H Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital, Inc

Memphis, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Children's Cancer and Hematology Center

Houston, Texas, United States

Jewish General Hospital

Québec, Montreal, Canada

Countries

United States; Canada

Other Identifiers

SNDX-5613-0702

Identifier Type: -

Identifier Source: org_study_id