Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

NCT06177067 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: RAVAMLNCI-2023-10509
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 10

Brief Summary

This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug. Primary Objective

• To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives
• Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).

Conditions

Refractory Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Acute Leukemia of Ambiguous Lineage

Outcome Measures

Primary Outcomes (1)

• The safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL

  The primary endpoint is the recommended phase 2 dose (RP2D) of revumenib + azacitidine + venetoclax.

  43 days from the start of therapy.

Secondary Outcomes (3)

• The rates of complete remission (CR)

  43 days from the start of therapy

• The rates of complete remission with incomplete count recovery (CRi)

  43 days from the start of therapy

• The overall survival of patients treated at the RP2D.

  1 year

Study Arms (1)

All Eligible Participants

EXPERIMENTAL

All eligible patients receive the following intervention: Revumenib, Venetoclax, Azacitidine, Intrathecal chemotherapy

Drug: Revumenib; Drug: Venetoclax; Drug: Azacitidine; Drug: intrathecal (IT) chemotherapy; Drug: Cytarabine; Drug: Methotrexate

Interventions

Revumenib DRUG

Given by mouth (capsule or liquid solution) or liquid solution by Nasogastric tube (NG) or Gastrostomy tube (G-tube)

Also known as: SNDX-5613

All Eligible Participants

Venetoclax DRUG

Given by mouth (tablet) or by NG or G-tube

Also known as: Venclextra®

All Eligible Participants

Azacitidine DRUG

Given intravenously (IV) infusion

Also known as: VIDAZA®, 5-azacitidine

All Eligible Participants

intrathecal (IT) chemotherapy DRUG

Given intrathecal (IT)

Also known as: ITMHA, methotrexate/hydrocortisone/cytarabine

All Eligible Participants

Cytarabine DRUG

Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.

Also known as: Ara-C, Cytosar®

All Eligible Participants

Methotrexate DRUG

Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.

Also known as: MTX, Trexall®

All Eligible Participants

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.
• However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
• Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214
• Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
• QTcF \< 480 msec (average of triplicate)
• Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
• Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
• At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
• Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
• For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
• Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
• Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
• Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.

You may not qualify if:

• Patients who are pregnant or breastfeeding are not eligible.
• Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
• Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Syndax Pharmaceuticals: collaborator

Study Sites (10)

Rady Children's Hospital

San Diego, California, 92132, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

RECRUITING

Children's Mercy Hospital of Kansas City

Kansas City, Missouri, 64108, United States

RECRUITING

Memorial Sloan- Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

UT Southwestern/Simmons Cancer Center

Dallas, Texas, 75390, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute

Interventions

revumenib; venetoclax; Azacitidine; Drug Therapy; Methotrexate; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Therapeutics; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Arabinonucleosides

Study Officials

• Hiroto Inaba, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hiroto Inaba, MD, PhD

CONTACT

888-226-4343; referralinfo@stjude.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

Model Details: Participants with relapsed or refractory acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) who meet the eligibility criteria.

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: December 20, 2023
• Study Start: April 19, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (10)