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

NCT05326516 | Completed Phase 1 FDA Drug

• 1 other identifier: SNDX-5613-0702
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 11

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

Keywords

SNDX-5613; AUGMENT; KMT2A/MLL Gene Rearrangement; Nucleophosmin 1 Mutation; NPM1; Nucleoporin 98; NUP98; Menin; Revumenib

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities From Revumenib

  Day 1 through up to 30 days after last dose of study intervention

• Number of Participants With Treatment-emergent Adverse Events

  Day 1 through up to 30 days after last dose of study intervention

Secondary Outcomes (3)

• Maximum Plasma Concentration (Cmax) of Revumenib

  Predose through up to 6 hours postdose

• Area Under The Plasma Concentration Versus Time Curve From Time 0 To t (AUC0-t) Of Revumenib

  Predose through up to 6 hours postdose

• Area Under The Concentration Versus Time Curve From Time 0 To 24 Hours (AUC0-24) Of Revumenib

  Predose through up to 6 hours postdose

Study Arms (2)

Revumenib and Chemotherapy Regimen 1

EXPERIMENTAL

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.

Drug: Revumenib; Drug: Chemotherapy Regimen 1

Revumenib and Chemotherapy Regimen 2

EXPERIMENTAL

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.

Drug: Revumenib; Drug: Chemotherapy Regimen 2

Interventions

Revumenib DRUG

Participants will receive revumenib until meeting criteria for discontinuation.

Also known as: SNDX-5613

Revumenib and Chemotherapy Regimen 1; Revumenib and Chemotherapy Regimen 2

Chemotherapy Regimen 1 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 1

Chemotherapy Regimen 2 DRUG

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

Revumenib and Chemotherapy Regimen 2

Eligibility Criteria

• Age: 30 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (11)

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

San Francisco, California, 94158, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10021, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital, Inc

Memphis, Tennessee, 38105, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Cancer and Hematology Center

Houston, Texas, 77030, United States

Location

Jewish General Hospital

Québec, Montreal, QC H3T 1E2, Canada

Location

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute

Interventions

revumenib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Study Officials

• Nicole McNeer, MD, PhD

  Syndax Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: The study will use a Bayesian optimal interval (BOIN) design to evaluate the doses and determine the maximum tolerated dose.

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 13, 2022
• Study Start: March 9, 2022
• Primary Completion: July 29, 2024
• Study Completion: July 29, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (10)