Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant

NCT06575296 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23520NCI-2024-06738P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, best dose and effectiveness of revumenib in treating patients with acute leukemia after allogeneic stem cell transplant. Revumenib is in a class of medications called menin inhibitors. Revumenib targets and binds to the protein menin, thereby preventing the interaction between menin and the mixed lineage leukemia protein. Disrupting this interaction prevents the activation of specific genes that fuel the development of leukemia cells and inhibits the survival, growth, and production of certain kinds of leukemia cells. Giving revumenib may be safe, tolerable, and/or effective in treating patients with acute leukemia after allogeneic stem cell transplant.

Conditions

Acute Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Childhood Acute Leukemia; Childhood Acute Leukemia of Ambiguous Lineage; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will evaluate toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5, including dose limiting toxicity (DLT). The toxicity/adverse event information recorded on each subject will include type, severity, duration, and attribution/association with the study regimen and DLT occurrence. Tables will be constructed to summarize the observed incidence, severity, and type of toxicity, including, but not limited to infections, other adverse events of special interest, and serious adverse events.

  Start of protocol therapy up to 2 years

Secondary Outcomes (10)

• Molecular response

  Up to 2 years

• Overall survival (OS)

  Start of protocol therapy to death, assessed up to 2 years

• Relapse free survival (RFS)

  Start of protocol therapy to relapse/progression or death, assessed up to 2 years

• Graft versus host disease (GVHD)-free/relapse survival (GRFS)

  Start of protocol therapy to first observation of developing grade 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse/progression, or death, assessed up to 2 years

• Cumulative incidence of relapse/progression

  Start of protocol therapy to relapse/progression, assessed up to 2 years

Study Arms (1)

Treatment (revumenib)

EXPERIMENTAL

Starting 50-150 days after alloHCT, patients receive revumenib PO QD or every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy during screening and may undergo ECHO during screening and as clinically indicated. Patients also undergo bone marrow aspiration and collection of blood samples throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography; Other: Electronic Health Record Review; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Revumenib

Interventions

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (revumenib)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (revumenib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (revumenib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (revumenib)

Revumenib DRUG

Given PO

Also known as: Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613, Menin-MLL Inhibitor SNDX-5613, Menin-MLL Interaction Inhibitor SNDX-5613, SNDX 5613, SNDX-5613, SNDX5613

Treatment (revumenib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (revumenib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (revumenib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (revumenib)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PATIENTS WHO ARE SCHEDULED TO UNDERGO HEMATOPOIETIC CELL TRANSPLANTATION (HCT) OR THOSE WHO HAVE UNDERGONE HCT: Documented informed consent of the participant and/or legally authorized representative
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Agreement to allow the use of archival tissue from diagnostic tumor biopsies; if unavailable, exceptions may be granted with study principal investigator (PI) approval
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant is willing and able to adhere to the study visit schedule and other protocol requirements
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Age: \>= 2 years
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Have a date for transplant within the next 4 weeks or have received transplant within the last 4 months
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant was diagnosed with an acute leukemia as defined by the World Health Organization (WHO) 5th edition criteria for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia with ambiguous lineage
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant must meet one of the following disease characteristics:
• Confirmed NPM1m AML with at least one of the following additional characteristics
• FLT3-ITD co-mutation
• Pre-transplant MRD+ disease by flow cytometry or real time polymerase chain reaction (qPCR)
• Requires more than one AML induction regimen to acquire complete response (CR)1
• In second or later complete remission
• Confirmed KMT2Ar acute leukemia obtained by fluorescence in situ hybridization (11q23 MLL-break apart fluorescence in situ hybridization \[FISH\]) or next-generation sequencing (NGS)
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Any donor (sibling, unrelated, mismatched related/unrelated, cord and haploidentical) or graft source (peripheral blood \[PB\] stem cell or bone marrow \[BM\]) will be included
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Conditioning regimen: investigator's choice based on center guidelines

You may not qualify if:

• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prior diagnosis of acute promyelocytic leukemia
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib cycle 1
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients requiring the concurrent use of medications known or suspected to prolong the QT/corrected QT (QTc) interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, azoles)
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
• PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
• PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant has detectable human immunodeficiency virus (HIV) viral load within the previous 6 months (must have viral load testing prior to study enrollment if participant has a known history of HIV 1/2 antibodies)
• PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Active uncontrolled hepatitis B or C, defined as hepatitis B or C virus (HBV/HCV) surface antigen positive and HBV/HCV core antibody positive, with positive HBV/HCV deoxyribonucleic acid (DNA), or HBV/HCV positive core antibody alone with positive HBV/HCV DNA
• PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Hepatitis C, defined as positive HCV antibody with reflex to positive HCV ribonucleic acid (RNA)
• PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Other active malignancy; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Active grade II-IV acute GVHD, chronic GVHD (moderate or severe) and/or requiring systemic steroids with prednisone dose equivalent of \>= 0.25mg/kg within 4 weeks of revumenib administration
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib in cycle 1
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, and azoles)
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Female participant who is pregnant or lactating
• CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has a malabsorption syndrome or other condition that precludes enteral route of administration

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

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

Interventions

Specimen Handling; Biopsy; revumenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Brian Ball, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Ball, MD

CONTACT

626-218-2405; brball@coh.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 28, 2024
• Study Start: December 6, 2024
• Primary Completion (Estimated): April 29, 2028
• Study Completion (Estimated): April 29, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)