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

NCT ID: NCT06177067

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-19

Study Completion Date

2027-04-30

Brief Summary

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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).

Detailed Description

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Patients will receive revumenib + azacitidine + venetoclax in a dose-escalation fashion. The protocol starts at dose level 1. If there are no dose limiting toxicities at dose level 1, then patients will be treated at dose level 2, which equates to the dose of revumenib increasing from 65 to 95 mg/m\^2 while the venetoclax exposure remains the same at 21 days. Alternatively, if there are dose limiting toxicities at dose level 1, then the dose level will be deescalated to dose level -1, which equates to the length of exposure of venetoclax being decreased from 21 days to 14 days, while the dose of revumenib stays at 65 mg/m\^2. The doses of azacitidine will remain constant at all dose levels.

For patients whose primary physician considers that single agent revumenib is beneficial (e.g., transition to hematopoietic cell transplant), revumenib can be continued after discussing with study principal investigator. Patients who undergo HCT will be taken off therapy at the time of HCT, but will remain on study. Post-transplant therapy will be determined by the HCT physician.

Patients who do not go on to receive an HCT, may continue to receive revumenib, venetoclax and azacitidine as long as their primary physician considers it beneficial and there are no unacceptable side effects.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Participants with relapsed or refractory acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) who meet the eligibility criteria.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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All Eligible Participants

All eligible patients receive the following intervention:

Revumenib, Venetoclax, Azacitidine, Intrathecal chemotherapy

Group Type EXPERIMENTAL

Revumenib

Intervention Type DRUG

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

Venetoclax

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

Given intravenously (IV) infusion

intrathecal (IT) chemotherapy

Intervention Type DRUG

Given intrathecal (IT)

Cytarabine

Intervention Type DRUG

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

Methotrexate

Intervention Type DRUG

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

Interventions

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Revumenib

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

Intervention Type DRUG

Venetoclax

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

Intervention Type DRUG

Azacitidine

Given intravenously (IV) infusion

Intervention Type DRUG

intrathecal (IT) chemotherapy

Given intrathecal (IT)

Intervention Type DRUG

Cytarabine

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

Intervention Type DRUG

Methotrexate

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

Intervention Type DRUG

Other Intervention Names

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SNDX-5613 Venclextra® VIDAZA® 5-azacitidine ITMHA methotrexate/hydrocortisone/cytarabine Ara-C Cytosar® MTX Trexall®

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syndax Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hiroto Inaba, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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Rady Children's Hospital

San Diego, California, United States

Site Status RECRUITING

Children's Mercy Hospital of Kansas City

Kansas City, Missouri, United States

Site Status RECRUITING

Memorial Sloan- Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

UT Southwestern/Simmons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Hiroto Inaba, MD, PhD

Role: CONTACT

Phone: 866-278-5833

Email: [email protected]

Facility Contacts

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Dennis Kuo, MD

Role: primary

Keith August, MD

Role: primary

Maria-Luisa Sulis, MD

Role: primary

Lauren Pommert, MD

Role: primary

Sarah Tasian, MD

Role: primary

Hiroto Inaba, MD, PhD

Role: primary

Kathleen Ludwig, MD

Role: primary

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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NCI-2023-10509

Identifier Type: REGISTRY

Identifier Source: secondary_id

RAVAML

Identifier Type: -

Identifier Source: org_study_id