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.

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.