Venetoclax combined with chemotherapy for children with acute myeloid leukemia

A Collaboration Phase 2 Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia

This study is testing if adding venetoclax to standard chemotherapy can help children with acute myeloid leukemia feel better and improve their chances of recovery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 29 Days to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (other)
• Drugs / interventions: chemotherapy, gemtuzumab, gilteritinib, fludarabine
• Locations: 6 sites (Madera, California and 5 other locations)
• Trial ID: NCT05955261 on ClinicalTrials.gov

What this trial studies

This phase 2 study investigates the safety and effectiveness of venetoclax when used alongside standard chemotherapy in pediatric patients diagnosed with acute myeloid leukemia (AML). The study aims to determine how well patients tolerate this combination treatment and to measure the rate of minimal residual disease negativity after one course of therapy. Treatment plans will be tailored based on the genetic characteristics of the patients and their response to therapy, with different chemotherapy courses for low, intermediate, and high-risk patients. The study will also evaluate overall survival and event-free survival rates among participants.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 28 days to 22 years with newly diagnosed acute myeloid leukemia.

Not a fit: Patients with prior therapy for AML or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve remission rates and overall survival for children with acute myeloid leukemia.

How similar studies have performed: Other studies have shown promising results with venetoclax in adult populations, but this specific combination in pediatric patients is novel.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of AML fulfilling the criteria of the WHO classification of myeloid neoplasms or \< 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality or myeloid sarcoma or primary myelodysplastic syndrome (MDS) with ≥ 10% blasts or a complete blood count with the presence of at least 1,000 blasts/μL (e.g., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count ≥ 5,000/μL with ≥ 20% blasts
* Age \> 28 days and \< 22 years
* No prior therapy for this malignancy except for one dose of intrathecal therapy and hydroxyurea or low-dose cytarabine (≤ 200 mg/m\^2 per day for ≤ 7 days)
* Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment
* Male and female participants of reproductive potential must agree to use an effective contraceptive method during the study and for 6 months after study treatment
* Written informed consent from the patient and/or parent/legal guardian
* Direct bilirubin ≤ 1.5 x institutional upper limit of normal

Exclusion Criteria:

* Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
* Uncontrolled systemic fungal, bacterial, or viral infection or significant concurrent disease that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results
* Prior exposure to any dose of anthracycline or anthracenedione
* Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of enrollment
* Patients may not receive moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) within 3 days of enrollment.

Where this trial is running

Madera, California and 5 other locations

• Valley Children's Hospital — Madera, California, United States (RECRUITING)
• Rady Children's Hospital-San Diego — San Diego, California, United States (RECRUITING)
• Novant Health Presbyterian Medical Center — Charlotte, North Carolina, United States (RECRUITING)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (RECRUITING)
• St. Jude Children's Research Hospital — Memphis, Tennessee, 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: Acute Myeloid Leukemia