Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Anti-Inflammatory Agents

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Pharmaceutical Solutions

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Cytarabine

Venetoclax

Azacitidine

Methotrexate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Folinic Acid

Folate

Vitamin B9

All eligible patients receive the following intervention:

Revumenib, Venetoclax, Azacitidine, Intrathecal chemotherapy

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

Revumenib

intrathecal (IT) chemotherapy

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

Hiroto Inaba, MD, PhD

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).

Patients will receive revumenib + azacitidine + venetoclax in a dose-escalation fashion. The doses of revumenib and azacitidine will remain constant, while the duration of exposure to venetoclax will be escalated or de-escalated. Patients may continue to receive therapy if there is clinical benefit and no unacceptable toxicity.

Patients who achieve complete response (CR) or Complete remission with incomplete blood count recovery (CRi) and subsequently undergo hematopoietic cell transplant (HCT) may remain on study. Revumenib, with or without azacitidine and venetoclax, may be resumed after transplant if the patient is at least 60 days post-transplant, remains in CR or CRi, has engrafted, and does not have Grade ≥2 acute graft versus host disease (GVHD). In the absence of toxicity, revumenib may be continued for a maximum of 12 months.

Patients are followed for 30 days after completion of study treatment.

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

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

A Phase 1 Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

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

CR is defined as bone marrow with \< 5% blasts confirmed by flow cytometry, ANC ≥500/μL and platelets ≥50,000/μL without transfusions, and no evidence of extramedullary disease.

CRi is defined as bone marrow with \<5% blasts confirmed by flow cytometry and ANC \<500/μL or platelets \<50,000/μL without transfusions

Kaplan-Meier estimates with 95% confidence intervals will be used to describe overall survival.

Syndax Pharmaceuticals

St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for intrathecal (it) chemotherapy