a study of the safety and pharmacokinetics of venetoclax in pediatric and young adult patients with relapsed or refractory malignancies

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

Summary: 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 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.

Keywords: cancer venetoclax pediatric relapsed or refractory venclexta