M13-833: A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies

Why are we doing this research?

PURPOSE:

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.

Study Type: Interventional
Intervention Model: Single Group Assignment
Masking: None

Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 1 Year to 25 Years

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.

Conditions

  • Leukemia ALL Relapse
  • Leukemia AML Relapse
  • Adult - Leukemia ALL Relapse
  • Adult - Leukemia AML Relapse
  • Lymphoma Non Hodgkin Relapse
  • Adult - Lymphoma Non Hodgkin Relapse
  • Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Ewing Relapse
  • Sarcoma Ewing Relapse
  • Sarcoma Rhabdomyosarcoma Relapse
  • Adult - Sarcoma Rhabdomyosarcoma Relapse
  • Neuroblastoma Relapse - Refractory
  • Adult - Neuroblastoma Relapse - Refractory
  • Liver Relapse - Refractory
  • Adult - Liver Relapse - Refractory
  • Kidney Relapse - Refractory
  • Adult - Kidney Relapse - Refractory
  • Solid Tumor Retinoblastoma Relapse - Refractory
  • Adult - Solid Tumor Retinoblastoma Relapse - Refractory
  • Solid Tumor Melanoma Relapse - Refractory
  • Adult - Solid Tumor Melanoma Relapse - Refractory
  • Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Adult - Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Solid Tumors - All Other
  • Solid Tumors - All Other
  • Adult - Solid Tumors - All Other

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org