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

NCT03181126 | Completed Phase 1 FDA Drug

• 1 other identifier: M16-106
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 15

Brief 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.

Conditions

Acute Lymphoblastic Leukemia (ALL); Lymphoblastic Lymphoma

Keywords

Relapsed of Refractory Acute Lymphoblastic Leukemia; Cancer; Venetoclax; Navitoclax

Outcome Measures

Primary Outcomes (5)

• Cmax of Venetoclax + Navitoclax

  Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax

  Up to approximately 9 months

• AUC of Venetoclax + Navitoclax

  Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax

  Up to approximately 9 months

• Tmax of Venetoclax + Navitoclax

  Time to Cmax (Tmax) of Venetoclax + Navitoclax

  Up to approximately 9 months

• CL/F of Venetoclax + Navitoclax

  Apparent oral clearance (CL/F) of venetoclax + navitoclax

  Up to approximately 9 months

• Number of participants with dose-limiting toxicities (DLT)

  A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.

  Up to approximately 28 days after initial dose of study drug

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Up to 9 months after the last subject has enrolled into the study

• Partial Response (PR) rate

  Up to 9 months after the last subject has enrolled into the study

• Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy

  Up to 9 months after the last subject has enrolled into the study

• Overall survival (OS)

  Up to 9 months after the last subject has enrolled into the study

• Objective response rate (ORR)

  Up to 9 months after the last subject has enrolled into the study

Study Arms (1)

Venetoclax + Navitoclax + Chemotherapy

EXPERIMENTAL

Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase \[or any other forms of asparaginase\], vincristine, dexamethasone) and tyrosine kinase inhibitor \[TKI, if applicable\]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.

Drug: Navitoclax; Drug: Chemotherapy; Drug: Venetoclax

Interventions

Navitoclax DRUG

tablet

Also known as: ABT-263

Venetoclax + Navitoclax + Chemotherapy

Chemotherapy DRUG

peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)

Venetoclax + Navitoclax + Chemotherapy

Venetoclax DRUG

tablet

Also known as: ABT-199 GDC-0199

Venetoclax + Navitoclax + Chemotherapy

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (15)

City of Hope /ID# 169029

Duarte, California, 91010, United States

Location

LPCH Stanford /ID# 163337

Palo Alto, California, 94304, United States

Location

University of Chicago /ID# 163369

Chicago, Illinois, 60637, United States

Location

Washington University-School of Medicine /ID# 165689

St Louis, Missouri, 63110, United States

Location

Univ NC Chapel Hill /ID# 163509

Chapel Hill, North Carolina, 27514-4220, United States

Location

Cincinnati Children's Hospital /ID# 164619

Cincinnati, Ohio, 45229, United States

Location

Nationwide Childrens Hospital /ID# 163372

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University /ID# 165690

Portland, Oregon, 97239, United States

Location

St Jude Children's Research Hospital /ID# 163335

Memphis, Tennessee, 38105, United States

Location

UT Southwestern Medical Center /ID# 163346

Dallas, Texas, 75390-7208, United States

Location

MD Anderson Cancer Center at Texas Medical Center /ID# 163327

Houston, Texas, 77030-4000, United States

Location

University of Wisconsin-Madiso /ID# 165691

Madison, Wisconsin, 53705, United States

Location

Alfred Hospital /ID# 169576

Melbourne, Victoria, 3004, Australia

Location

Victorian Comprehensive Cancer /ID# 165710

Melbourne, Victoria, 3050, Australia

Location

Royal Children's Hospital /ID# 163322

Melbourne, Victoria, 3052, Australia

Location

Related Publications (1)

• Badawi M, Gopalakrishnan S, Engelhardt B, Palenski T, Karol SE, Rubnitz JE, Menon R, Salem AH. Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships. Clin Ther. 2024 Oct;46(10):759-767. doi: 10.1016/j.clinthera.2024.09.008. Epub 2024 Oct 5.

  PMID: 39368878 DERIVED

Related Links

• clinical study report synopsis

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms

Interventions

navitoclax; Drug Therapy; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: June 8, 2017
• Study Start: November 27, 2017
• Primary Completion: November 11, 2020
• Study Completion: November 14, 2020
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

US (12); AU (3)