A Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies

May 19, 2023 updated by: AbbVie

A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies

An open-label, global, multi-center study to evaluate the safety and pharmacokinetics of venetoclax monotherapy, to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of venetoclax in pediatric and young adult participants with relapsed or refractory malignancies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

143

Phase

  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Sydney Children's Hospital /ID# 163148
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Queensland Children's Hospital /ID# 163146
    • South Australia
      • North Adelaide, South Australia, Australia, 5006
        • Women and Childrens Hospital /ID# 163147
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital /ID# 163104
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children /ID# 163726
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine /ID# 163725
  • France
      • Paris, France, 75012
        • AP-HP - Hopital Armand-Trousseau /ID# 163728
      • Paris, France, 75019
        • Robert Debre Hopital, FR /ID# 161464
      • Toulouse CEDEX 9, France, 31059
        • CHU Toulouse - Hôpital des enfants /ID# 163727
    • Bouches-du-Rhone
      • Marseille CEDEX 05, Bouches-du-Rhone, France, 13385
        • AP-HM - Hopital de la Timone /ID# 161465
    • Rhone
      • Lyon CEDEX 08, Rhone, France, 69373
        • Centre Leon Berard /ID# 163707
  • Germany
      • Berlin, Germany, 13353
        • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 161730
      • Essen, Germany, 45147
        • Universitaetsklinikum Essen /ID# 164207
    • Baden-Wuerttemberg
      • Freiburg, Baden-Wuerttemberg, Germany, 79106
        • Universitaetsklinikum Freiburg /ID# 164206
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161729
  • Netherlands
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC - Sophia /ID# 161579
      • Utrecht, Netherlands, 3584 CS
        • Prinses Maxima Centrum /ID# 162670
  • Switzerland
    • Zuerich
      • Zurich, Zuerich, Switzerland, 8032
        • Kinderspital Zurich - Eleonorenstiftung /ID# 163037
  • United Kingdom
      • Newcastle Upon Tyne, United Kingdom, NE7 7DN
        • The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 162938
    • London, City Of
      • London, London, City Of, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children /ID# 169238
  • United States
    • California
      • San Francisco, California, United States, 94143-2204
        • Univ California, San Francisco /ID# 163460
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado /ID# 161551
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlan /ID# 161552
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute /ID# 163440
    • New York
      • New York, New York, United States, 10065-6007
        • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 163444
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital /ID# 161550
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia /ID# 163445
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St Jude Children's Research Hospital /ID# 163447
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's /ID# 164399
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital /ID# 163459
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226-3522
        • Medical College of Wisconsin /ID# 163461

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must have relapsed or refractory cancer.
  • Participants must have adequate hepatic and kidney function.
  • Participants less than or equal to 16 years of age must have performance status of Lansky greater than or equal to 50% and participants greater than 16 years of age must have performance status of Karnofsky greater than or equal to 50%.
  • Participants with solid tumors (with the exception of neuroblastoma) must have adequate bone marrow function in Part 1.
  • For the fifth cohort during Part 2 Cohort Expansion, participants with solid tumors must have evidence of BCL-2 expression (except participants with TCF3-HLF ALL).

Exclusion Criteria:

  • Participants with primary brain tumors or disease metastatic to the brain.
  • Participants who have central nervous system (CNS) disease with cranial involvement that requires radiation.

  • Participants who have received any of the following within the listed time frame, prior to the first dose of study drug

    • Inotuzumab ozogamicin or gemtuzumab ozogamicin within 30 days
    • Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days or 5 half-lives whichever is shorter.
    • CAR-T infusion or other cellular therapy within 30 days
    • Anticancer therapy including chemotherapy, radiation therapy, targeted small molecule agents, investigational agents within 14 days or 5 half-lives, whichever is shorter (Exceptions: Ph+ALL participants on Tyrosine Kinase Inhibitor (TKI) at Screening may enroll and remain on TKI therapy to control disease and TCF3-HLF ALL participants are allowed to have received chemotherapy within 14 days or 5 half-lives, whichever is shorter).
    • Steroid therapy for anti-neoplastic intent within 5 days (with the exception of TCF3-HLF ALL participants).
    • Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose)
  • Participants who are less than 100 days post-transplant, or greater than or equal to 100 days post-transplant with active graft versus host disease (GVHD), or are receiving immunosuppressant therapy within 7 days prior to first dose of study drug.
  • Participants who are less than 6 weeks post-131 I-metaiodobenzylguanidine (mIBG) therapy.

  • Participants who have received the following within 7 days prior to the first dose of study drug:

    • Strong and moderate Cytochrome P450 3A (CYP3A) inhibitors (Part 1 Dose Determination);
    • Strong and moderate CYP3A inducers (Part 1 Dose Determination and Part 2 Cohort Expansion).
  • Participants who have not recovered from clinically significant adverse effect(s)/toxicity(s) of the previous therapy (Exception: Chemotherapy induced side effects that are expected to return to baseline in TCF3-HLF ALL participants).
  • Participants who have active, uncontrolled infections.

  • Participants with malabsorption syndrome or any other condition that precludes enteral administration.

    • Participants with recent positive test for SARS-CoV-2 (COVID-19) and no follow up test with negative result cannot be enrolled. Participants with contact to persons with COVID-19 and participants with signs and symptoms for COVID-19 infection must be tested before enrolling.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venetoclax with or without chemotherapy
Venetoclax administered orally once daily (QD) with various doses and dosing regimens with or without chemotherapy at the discretion of the investigator. Allowed chemotherapy regimens as outlined in the study protocol.
Drug: chemotherapy
Dexamethasone and/or vincristine and/or pegasparaginase OR cytarabine and/or etoposide and/or pegasparaginase; tyrosine kinase inhibitor; cytarabine OR azacitidine OR decitabine; rituximab and/or dexamethasone and/or vincristine; cyclophosphamide and/or topotecan
Drug: venetoclax
Oral tablet for participants; Tablet for oral suspension (participants who cannot swallow a tablet)
Other Names:
  • Venclexta
  • ABT-199
  • GDC-0199

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Adverse Events
Time Frame: Up to 9 months
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.
Up to 9 months
Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy
Time Frame: First 21 days venetoclax monotherapy
A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol.
First 21 days venetoclax monotherapy
Recommended Phase 2 dose (RPTD) of Venetoclax
Time Frame: First 21 days venetoclax monotherapy
Venetoclax RPTD is the dose determined based on adverse event reporting and dose-limiting toxicity information from all participants.
First 21 days venetoclax monotherapy
Cmax of Venetoclax
Time Frame: Up to approximately 2 weeks
Maximum plasma concentration (Cmax) of venetoclax.
Up to approximately 2 weeks
Tmax of venetoclax
Time Frame: Up to approximately 2 weeks
Time to maximum plasma concentration (Tmax) of venetoclax.
Up to approximately 2 weeks
AUC0-24 Post-Dose of Venetoclax
Time Frame: Up to approximately 2 weeks
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Up to approximately 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to 9 months
ORR is defined as the proportion of participants who achieved a response according to established criteria described in detail in the study protocol.
Up to 9 months
Partial Response (PR) Rate
Time Frame: Up to 9 months
PR is defined according to established criteria for each tumor type and is described in detail within the study protocol.
Up to 9 months
Complete Response (CR) Rate
Time Frame: Up to 9 months
CR is defined according to established criteria for each tumor type and is described in detail within the study protocol.
Up to 9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Collaborators

Roche-Genentech

Investigators

  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 8, 2017

Primary Completion (Actual)

April 19, 2023

Study Completion (Actual)

April 19, 2023

Study Registration Dates

First Submitted

July 31, 2017

First Submitted That Met QC Criteria

July 31, 2017

First Posted (Actual)

August 2, 2017

Study Record Updates

Last Update Posted (Actual)

May 22, 2023

Last Update Submitted That Met QC Criteria

May 19, 2023

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M13-833
  • 2017-000439-14 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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