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

NCT03236857

CompletedPhase 1

Sponsor: AbbVie

Conditions: Malignancies, Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Non-Hodgkin's Lymphoma, Neuroblastoma

Interventions: chemotherapy, venetoclax

Countries: United States, Australia, Canada, France, Germany, Netherlands, Switzerland, United Kingdom

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.

Eligibility overview

Sex: ALL

Age: 0 Years to 25 Years

Healthy volunteers: No

Study type: INTERVENTIONAL

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 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.
Locations (31)
  • San Francisco, California, United States
  • Aurora, Colorado, United States
  • Atlanta, Georgia, United States
  • Boston, Massachusetts, United States
  • New York, New York, United States
  • Cincinnati, Ohio, United States
  • Philadelphia, Pennsylvania, United States
  • Memphis, Tennessee, United States
  • Salt Lake City, Utah, United States
  • Seattle, Washington, United States
  • Milwaukee, Wisconsin, United States
  • Randwick, New South Wales, Australia
  • South Brisbane, Queensland, Australia
  • North Adelaide, South Australia, Australia
  • Parkville, Victoria, Australia
  • Toronto, Ontario, Canada
  • Montreal, Quebec, Canada
  • Marseille, Bouches-du-Rhone, France
  • Lyon, Rhone, France
  • Paris, France
  • Paris, France
  • Toulouse, France
  • Freiburg im Breisgau, Baden-Wurttemberg, Germany
  • Kiel, Schleswig-Holstein, Germany
  • Berlin, Germany
  • Essen, Germany
  • Rotterdam, Netherlands
  • Utrecht, Netherlands
  • Zurich, Canton of Zurich, Switzerland
  • London, London, City of, United Kingdom
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