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

NCT ID: NCT03181126

Last Updated: 2021-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-27

Study Completion Date

2020-11-14

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Lymphoblastic Leukemia (ALL) Lymphoblastic Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Venetoclax + Navitoclax + Chemotherapy

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.

Group Type EXPERIMENTAL

Navitoclax

Intervention Type DRUG

tablet

Chemotherapy

Intervention Type 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

Intervention Type DRUG

tablet

Interventions

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Navitoclax

tablet

Intervention Type DRUG

Chemotherapy

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

Intervention Type DRUG

Venetoclax

tablet

Intervention Type DRUG

Other Intervention Names

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ABT-263 ABT-199 GDC-0199

Eligibility Criteria

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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.
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

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City of Hope /ID# 169029

Duarte, California, United States

Site Status

LPCH Stanford /ID# 163337

Palo Alto, California, United States

Site Status

University of Chicago /ID# 163369

Chicago, Illinois, United States

Site Status

Washington University-School of Medicine /ID# 165689

St Louis, Missouri, United States

Site Status

Univ NC Chapel Hill /ID# 163509

Chapel Hill, North Carolina, United States

Site Status

Cincinnati Children's Hospital /ID# 164619

Cincinnati, Ohio, United States

Site Status

Nationwide Childrens Hospital /ID# 163372

Columbus, Ohio, United States

Site Status

Oregon Health and Science University /ID# 165690

Portland, Oregon, United States

Site Status

St Jude Children's Research Hospital /ID# 163335

Memphis, Tennessee, United States

Site Status

UT Southwestern Medical Center /ID# 163346

Dallas, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

University of Wisconsin-Madiso /ID# 165691

Madison, Wisconsin, United States

Site Status

Alfred Hospital /ID# 169576

Melbourne, Victoria, Australia

Site Status

Victorian Comprehensive Cancer /ID# 165710

Melbourne, Victoria, Australia

Site Status

Royal Children's Hospital /ID# 163322

Melbourne, Victoria, Australia

Site Status

Countries

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United States Australia

References

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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.

Reference Type DERIVED
PMID: 39368878 (View on PubMed)

Related Links

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Other Identifiers

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M16-106

Identifier Type: -

Identifier Source: org_study_id