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

Status: Active

Description

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.

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: Active
Name Not Available
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Name Not Available

Ohio

Columbus
Nationwide Children's Hospital
Status: Active
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Tennessee

Memphis
St. Jude Children's Research Hospital
Status: Temporarily closed to accrual
Contact: Jeffrey E. Rubnitz
Phone: 901-595-2388
Email: jeffrey.rubnitz@stjude.org

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
Email: marcella.aguilar@utsouthwestern.edu
Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Abbvie

Trial IDs

Primary ID M16-106
Secondary IDs NCI-2018-00045
Clinicaltrials.gov ID NCT03181126