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

Part of paid clinical trials in San Diego, California.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT04898894
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Acute Leukemia of Ambiguous Lineage in Relapse
  • Acute Myeloid Leukemia, in Relapse
  • Refractory Acute Leukemia of Ambiguous Lineage
  • Refractory Acute Myeloid Leukemia

Eligibility Criteria

Sex
ALL
Age
2 Years - 30 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Given orally (PO)
  • Selinexor — DRUG
    Given Orally (PO)
  • Cytarabine — DRUG
    Given in to the vein (IV) or intrathecal (IT)
  • Fludarabine — DRUG
    Given in to the vein (IV) - Because of the ongoing nationwide shortage of fludarabine, this agent may be omitted during the dose expansion phase of the trial.
  • Filgrastim — BIOLOGICAL
    Given subcutaneous (SubQ, SC)
  • Methotrexate — DRUG
    Given intrathecal (IT)
  • methotrexate/hydrocortisone/cytarabine — DRUG
    Given intrathecal (IT)

Study Details

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.

Key Dates

Start date
Nov 15, 2021
Status verified
Apr 2026
Primary completion
Jul 12, 2023
Completion
Sep 30, 2027

Study Design

Enrollment
37 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment
    Dose Escalation Phase: Venetoclax plus selinexor will initially be given at dose level 1 in combination with intravenous (IV) cytarabine and fludarabine. Dosing of venetoclax and selinexor will be based on tolerability. Intrathecal (IT) chemotherapy (IT cytarabine, IT methotrexate, and IT methotrexate/hydrocortisone/cytarabine (MHA) are all acceptable) will be given. G-CSF SC may be given. Part 1 has been completed and RP2D has been determined to be Dose Level 2. All participants will be treated at Dose Level 2. Dose Expansion Phase: Two expansion cohorts will be treated at the recommended phase 2 dose (RP2D). Cohort A will include venetoclax-naïve patients, whereas Cohort B will include patients with prior exposure to venetoclax.

Primary Outcome Measure

The recommended phase 2 dose (RP2D) of venetoclax plus selinexor plus chemotherapy. [ Time Frame: 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. ]

Locations (8)

FacilityCityStateZIPSite coordinators
Rady Children's Hospital-San DiegoSan DiegoCalifornia92123-
Dana-Farber Cancer InstituteBostonMassachusetts02215-
Memorial Sloan-Kettering Cancer CenterNew YorkNew York10065-
Childrens Hospital of PhiladelphiaPhiladelphiaPennsylvania19104-
St. Jude Children's Research HospitalMemphisTennessee38105-
Vanderbilt University Medical CenterNashvilleTennessee37232-
UT Southwestern/Simmons Cancer CenterDallasTexas75390-
Cook Children's Medical CenterFort WorthTexas76104-

Find similar trials in San Diego, CA

By research site
Rady Children's Hospital-San Diego· San Diego, CADana-Farber Cancer Institute· Boston, MAMemorial Sloan-Kettering Cancer Center· New York, NYChildrens Hospital of Philadelphia· Philadelphia, PASt. Jude Children's Research Hospital· Memphis, TNVanderbilt University Medical Center· Nashville, TN

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