Combining revumenib, azacitidine, and venetoclax for treating pediatric and young adult patients with tough cases of 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

This study is testing a new combination of drugs to see if it can help young patients with tough cases of acute myeloid leukemia feel better and achieve remission.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 1 Year to 30 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 10 sites (San Diego, California and 9 other locations)
• Trial ID: NCT06177067 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and effectiveness of a new drug, revumenib, in combination with azacitidine and venetoclax for pediatric and young adult patients suffering from refractory or relapsed acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL). The approach involves a dose-escalation methodology to determine the maximum tolerated dose of the drug combination while monitoring for any adverse effects. Participants will receive treatment in a structured manner, with adjustments made based on their response and any side effects experienced. The study also aims to evaluate the rates of complete remission and overall survival among the participants.

Who should consider this trial

Good fit: Ideal candidates are pediatric and young adult patients with refractory or relapsed AML or ALAL who have specific genetic markers and adequate organ function.

Not a fit: Patients with leukemia types that do not meet the study criteria or those who have already undergone certain treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for young patients with difficult-to-treat forms of leukemia.

How similar studies have performed: Other studies have shown promise with similar drug combinations in treating leukemia, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria: Participants must have a diagnosis of AML or ALAL and meet the criteria below:

* 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.

Where this trial is running

San Diego, California and 9 other locations

• Rady Children's Hospital — San Diego, California, United States (Recruiting)
• Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
• Children's Mercy Hospital of Kansas City — Kansas City, Missouri, United States (Recruiting)
• Memorial Sloan- Kettering Cancer Center — New York, New York, United States (Recruiting)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
• UT Southwestern/Simmons Cancer Center — Dallas, Texas, United States (Recruiting)
• Cook Children's Medical Center — Fort Worth, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Hiroto Inaba, MD, PhD — St. Jude Children's Research Hospital
• Study coordinator: Hiroto Inaba, MD, PhD

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