A Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies

An open-label, global, multi-center study to evaluate the safety and pharmacokinetics of venetoclax monotherapy, to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of venetoclax in pediatric and young adult participants with relapsed or refractory malignancies.

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Site-responsible Investigators:

Contacts:

Eligibility Criteria

Inclusion Criteria:

  -  Participants must have relapsed or refractory cancer.

  -  Participants must have adequate hepatic and kidney function.

  -  Participants less than or equal to 16 years of age must have performance status of
     Lansky greater than or equal to 50% and participants greater than 16 years of age must
     have performance status of Karnofsky greater than 50%.

  -  Participants with solid tumors (with the exception of neuroblastoma) must have
     adequate bone marrow function in Part 1.

  -  For the fifth cohort during Part 2 Cohort Expansion, participants with solid tumors
     must have evidence of BCL-2 expression.

Exclusion Criteria:

  -  Participants with primary brain tumors or disease metastatic to the brain.

  -  For participants with leukemia, has overt central nervous system (CNS) disease (CNS 3
     status).

  -  Participants who have received any of the following within the listed time frame,
     prior to the first dose of study drug

       -  Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days

       -  CAR-T infusion or other cellular therapy within 30 days

       -  Anticancer therapy including blinatumomab or chemotherapy, radiation therapy,
  targeted small molecule agents, investigational agents within 14 days or 5
  half-lives, whichever is shorter

       -  Steroid therapy for anti-neoplastic intent within 5 days

       -  Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose)

  -  Participants who are less than 100 days post-transplant, or greater than or equal to
     100 days post-transplant with active graft versus host disease (GVHD), or are
     receiving immunosuppressant therapy within 7 days prior to first dose of study drug.

  -  Participants who are less than 6 weeks post-131 I-metaiodobenzylguanidine (mIBG)
     therapy.

  -  Participants who have received the following within 7 days prior to the first dose of
     study drug:

       -  Strong and moderate Cytochrome P450 3A (CYP3A) inhibitors (Part 1 Dose
  Determination);

       -  Strong and moderate CYP3A inducers (Part 1 Dose Determination and Part 2 Cohort
  Expansion).

  -  Participants who have not recovered from clinically significant adverse
     effect(s)/toxicity(s) of the previous therapy.

  -  Participants who have active, uncontrolled infections.

  -  Participants with malabsorption syndrome or any other condition that precludes enteral
     administration.