a study of venetoclax in combination with navitoclax and chemotherapy in subjects with relapsed/refractory acute lymphoblastic leukemia or relapsed/refractory lymphoblastic lymphoma

Conditions: Acute Lymphoblastic Leukemia (ALL); Lymphoblastic Lymphoma

Summary: this dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (all) or relapsed/refractory lymphoblastic lymphoma. a safety expansion cohort of approximately 20 patients may be enrolled in addition to the 50 participants in dose-escalation cohort.


Eligibility criteria:
inclusion criteria: * must have relapsed or refractory acute lymphoblastic leukemia (all) or relapsed or refractory lymphoblastic lymphoma (ll). refractory is defined as persistent disease after at least 2 courses of chemotherapy. * participants with all with philadelphia chromosome or with an abl class targetable fusion are eligible. * participants with ll must have radiographic evidence of disease * participants \<= 18 years of age who do not have a standard of care treatment option available. * must weigh greater than or equal to 20 kg. * must be able to swallow pills. * must have adequate hepatic and kidney function. * must have adequate performance status: * participants less than or equal to 16 years of age: lansky greater than or equal to 50 * participants greater than 16 years of age: karnofsky greater than or equal to 50 or eastern cooperative oncology group (ecog) less than 3. exclusion criteria: * participant has central nervous system (cns) disease with cranial involvement that requires radiation. * participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (gvhd), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug. * participants who have received any of the following prior to the first dose of study drug: * inotuzumab within 30 days (if participant received inotuzumab \> 30 days prior to day 1, must have alt, ast and bilirubin \< uln). * a biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days * car-t infusion or other cellular therapy within 30 days * any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter * exception: philadelphia chromosome (ph)+ all subjects on tkis at screening may enroll and remain on tyrosine kinase inhibitor (tki) therapy to control disease. participants on venetoclax at screening may enroll and remain on venetoclax. * steroid therapy for anti-neoplastic intent within 5 days * hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose) * a strong or moderate cyp3a inhibitor or inducer within 7 days * aspirin within 7 days, or 5 half-lives, whichever is longer * an excluded antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer * participants with malabsorption syndrome or any other condition that precludes enteral administration.

Keywords: relapsed of refractory acute lymphoblastic leukemia cancer venetoclax navitoclax