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

A Phase 1 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.

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 or equal to 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 (except participants with TCF3-HLF ALL).

Exclusion Criteria:

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

• Participants who have central nervous system (CNS) disease with cranial involvement that requires radiation.

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

  • Inotuzumab ozogamicin or gemtuzumab ozogamicin within 30 days
  • Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days or 5 half-lives whichever is shorter.
  • CAR-T infusion or other cellular therapy within 30 days
  • Anticancer therapy including chemotherapy, radiation therapy, targeted small molecule agents, investigational agents within 14 days or 5 half-lives, whichever is shorter (Exceptions: Ph+ALL participants on Tyrosine Kinase Inhibitor (TKI) at Screening may enroll and remain on TKI therapy to control disease and TCF3-HLF ALL participants are allowed to have received chemotherapy within 14 days or 5 half-lives, whichever is shorter).
  • Steroid therapy for anti-neoplastic intent within 5 days (with the exception of TCF3-HLF ALL participants).
  • 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 (Exception: Chemotherapy induced side effects that are expected to return to baseline in TCF3-HLF ALL participants).

• Participants who have active, uncontrolled infections.

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

  • Participants with recent positive test for SARS-CoV-2 (COVID-19) and no follow up test with negative result cannot be enrolled. Participants with contact to persons with COVID-19 and participants with signs and symptoms for COVID-19 infection must be tested before enrolling.