A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

• Status: Completed
• Trial end date: 2020-11-14
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AbbVie
• Treatments: Navitoclax; Venetoclax

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.