Clinical trial · Interventional
Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Leukemia of Ambiguous Lineage
A Phase I and Expansion Cohort Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia
NCT03194932CI-TRIAL-00063902completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The purpose of this study is to test the safety and determine the best dose of venetoclax and cytarabine when given with or without idarubicin in treating pediatric patients with acute myeloid leukemia (AML) that did not respond to treatment (refractory) or has come back after treatment (relapsed). PRIMARY OBJECTIVE: Determine a tolerable combination of venetoclax plus chemotherapy in pediatric patients with relapsed or refractory AML or acute leukemia of ambiguous lineage. The primary endpoints are the recommended phase 2 doses (RP2D) of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin. SECONDARY OBJECTIVE: Estimate the overall response rate to the combination of venetoclax and chemotherapy in pediatric patients with relapsed or refractor AML or acute leukemia of ambiguous lineage. The secondary endpoints are the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated at the RP2D.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Azacitidine | Drug | Azacitidine | ALIAS |
| Cytarabine | Drug | Cytarabine | ALIAS |
| Idarubicin | Drug | Idarubicin | ALIAS |
| Intrathecal Triple Therapy | Drug | — | UNRESOLVED |
| Venetoclax | Drug | Venetoclax | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment
- description
- In Part 1, venetoclax with cytarabine will initially be given at dose level 1 and escalated based on tolerability. Idarubicin will be given only at dose level 4. Note: Part 1 has been completed. Two expansion cohorts will be enrolled: * Cohort A will be a group of 12 participants receiving the recommended phase 2 doses (RP2D) of venetoclax plus cytarabine. * Cohort B will be a group of 12 participants receiving the RP2D of venetoclax plus cytarabine and idarubicin. Intrathecal Triple Therapy (ITMHA) will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly ITMHA beginning on day 8 until the cerebrospinal fluid becomes free of leukemia. Cohort C: Participants will receive venetoclax PO on days 1-21, azacitidine IV on days 1-7, and cytarabine Q12H on days 8-11.
- interventionNames
- Drug: Venetoclax
- Drug: Cytarabine
- Drug: Idarubicin
- Drug: Intrathecal Triple Therapy
- Drug: Azacitidine
Primary outcomes (1)
- measure
- Maximum tolerated combination (MTC)
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 2 Years
- Maximum age
- 20 Years
Show eligibility criteria text
Inclusion Criteria: * Participants must have a diagnosis of AML or acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia) and have refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy; or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. * Patients in all categories above must have ≥ 5% blasts in the bone marrow as assessed by morphology or ≥ 1 blasts in the bone marrow as assessed by flow cytometry. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood. In addition, patients in all categories must not be eligible to undergo curative therapy, such as immediate SCT, because of disease burden, time needed to identify a stem cell donor, or other reasons. \* Adequate organ function defined as the following: * Direct bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * AST (SGOT) and ALT (SGPT) ≤ 4 x ULN * Normal creatinine for age or a calculated creatinine clearance ≥ 60 mL/min/1.73 m2 * Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25% * St. Jude patients must be between 2 years and ≤ 21 years of age, on therapy (active patient), or within 3 years of completion of therapy. Patients treated at collaborating sites must be ≤ 24 years old. * Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are \> 16 years old. * Patients must have fully recovered from the acute effects of all prior therapy and cannot have evidence of graft-versus-host disease (GVHD) Exclusion Criteria: * Must not be pregnant or breastfeeding. Male or female of reproductive potential must agree to use effective contraception for the duration of study participation. * Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible. * Uncontrolled infection. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable. * Impairment of GI function or GI disease that may significantly alter the absorption of venetoclax.
References
Publications (3)
- DERIVEDDaniels KP, Pounds SB, Wu H, Wang L, Alexander TB, Budhraja A, Wolf J, Westover T, Mead PE, Mehr CM, Gupta SD, Lacayo NJ, Inaba H, Rees M, Pui CH, Opferman JT, Klco JM, Rubnitz JE, Karol SE. Venetoclax in combination with cytarabine with or without idarubicin or azacitidine in children, adolescents, and young adults with relapsed or refractory acute myeloid leukaemia (VENAML): a multicentre, phase 1 expansion study. Lancet Haematol. 2026 Aug;13(8):e545-e554. doi: 10.1016/S2352-3026(26)00136-5. Epub 2026 Jul 8. PMID 42419338
- DERIVEDBadawi M, Gopalakrishnan S, Engelhardt B, Palenski T, Karol SE, Rubnitz JE, Menon R, Salem AH. Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships. Clin Ther. 2024 Oct;46(10):759-767. doi: 10.1016/j.clinthera.2024.09.008. Epub 2024 Oct 5. PMID 39368878
- DERIVEDKarol SE, Alexander TB, Budhraja A, Pounds SB, Canavera K, Wang L, Wolf J, Klco JM, Mead PE, Das Gupta S, Kim SY, Salem AH, Palenski T, Lacayo NJ, Pui CH, Opferman JT, Rubnitz JE. Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study. Lancet Oncol. 2020 Apr;21(4):551-560. doi: 10.1016/S1470-2045(20)30060-7. Epub 2020 Mar 11. PMID 32171069