Active — Not RecruitingPhase 1

Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

United States37 participantsStarted 2021-11-15

Plain-language summary

The purpose of this study is to test the safety and determine the best dose of venetoclax and selinexor when given with chemotherapy drugs in treating pediatric and young adult patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that has come back (relapsed) or did not respond to treatment (refractory). Primary Objective * To determine the safety and tolerability of selinexor and venetoclax in combination with chemotherapy in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives * Describe the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated with selinexor and venetoclax in combination with chemotherapy at the recommended phase 2 dose (RP2D). * Describe the overall survival of patients treated at the RP2D. Exploratory Objectives * Explore associations between leukemia cell genomics, BCL2 family member protein quantification, BH3 profiling, and response to therapy as assessed by minimal residual disease (MRD) and variant clearance using cell-free deoxyribonucleic acid (DNA) (cfDNA). * Describe the quality of life of pediatric patients undergoing treatment with selinexor and venetoclax in combination with chemotherapy and explore associations of clinical factors with patient-reported quality of life outcomes. * Describe the clinical and genetic features associated with exceptional response to the combination of venetoclax and selinexor without the addition of chemotherapy.

Who can participate

Age range2 Years – 30 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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, OR * Early relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission and within one year of diagnosis, OR * Relapsed leukemia that is refractory to at least one course of salvage therapy (i.e., therapy given after the relapse has occurred), OR * Relapsed leukemia following HCT, OR * Second or greater relapse * Patients with late first relapses, defined as the re-appearance of leukemia after the achievement of remission and greater than one year of diagnosis, may be enrolled in the dose expansion portion of the study after safety data from the dose escalation portion is available. Patients must have ≥ 5% blasts in the bone marrow as assessed by morphology or flow cytometry. However, if flow cytometry cannot be performed or 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 in the blood. In addition, patients in all categories must not be eligible to undergo curative therapy, such as immediate HCT, because of disease burden, time to identify a stem cell donor, or other reasons. * Adequate organ function defined as the following: * Direct bilirubin ≤ 1…

What they're measuring

The recommended phase 2 dose (RP2D) of venetoclax plus selinexor plus chemotherapy.

Timeframe: For each patient, the monitoring time period for dose-limiting toxicity will extend for 35 days from receipt of the first dose of protocol-directed selinexor or venetoclax.

Number of patients treated

Timeframe: 35 days from the receipt of the first dose of protocol-directed selinexor or venetoclax

Number of patients who experience a Non-Hematologic dose limiting toxicity (DLT) during the dose escalation phase

Timeframe: Within 35 days of the first dose of chemotherapy

Number of patients who experience a Hematologic DLT during the dose escalation phase

Timeframe: From the start of chemotherapy up to day 43

Trial details

NCT IDNCT04898894

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-07-12

View on ClinicalTrials.gov More Acute Leukemia of Ambiguous Lineage in Relapse trials