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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03236857
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : September 26, 2019
Information provided by (Responsible Party):

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignancies Acute Lymphoblastic Leukemia (ALL) Acute Myeloid Leukemia (AML) Non-Hodgkin's Lymphoma Neuroblastoma Drug: chemotherapy Drug: venetoclax Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
Actual Study Start Date : November 8, 2017
Estimated Primary Completion Date : April 7, 2022
Estimated Study Completion Date : April 7, 2022

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:
  • ABT-199
  • GDC-0199

Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. Tmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Time to maximum plasma concentration (Tmax) of venetoclax

  5. Cmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Maximum plasma concentration (Cmax) of venetoclax

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 within 30 days
    • Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days
    • CAR-T infusion or other cellular therapy within 30 days
    • Anticancer therapy including blinatumomab or 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).
    • Steroid therapy for anti-neoplastic intent within 5 days
    • 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.
  • Participants who have active, uncontrolled infections.
  • Participants with malabsorption syndrome or any other condition that precludes enteral administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03236857

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Contact: ABBVIE CALL CENTER 847.283.8955

  Hide Study Locations
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United States, Arizona
Phoenix Children's Hospital /ID# 202022 Not yet recruiting
Phoenix, Arizona, United States, 85016-7710
United States, California
Univ California, San Francisco /ID# 163460 Not yet recruiting
San Francisco, California, United States, 94143-2204
United States, Colorado
Children's Hospital Colorado /ID# 161551 Recruiting
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlan /ID# 161552 Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute /ID# 163440 Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Mott Children's Hospital /ID# 211253 Not yet recruiting
Ann Arbor, Michigan, United States, 48109-4000
United States, New York
Memorial Sloan Kettering Cancer Center /ID# 163444 Recruiting
New York, New York, United States, 10065-6007
United States, Ohio
Cincinnati Children's Hospital /ID# 161550 Recruiting
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hosp Philadelphia /ID# 163445 Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Childrens Res Hosp /ID# 163447 Recruiting
Memphis, Tennessee, United States, 38105
United States, Utah
Primary Children's /ID# 164399 Recruiting
Salt Lake City, Utah, United States, 84113
United States, Washington
Seattle Children's Hospital /ID# 163459 Recruiting
Seattle, Washington, United States, 98105
United States, Wisconsin
Medical College of Wisconsin /ID# 163461 Recruiting
Milwaukee, Wisconsin, United States, 53226-3522
Australia, New South Wales
Sydney Children's Hospital /ID# 163148 Recruiting
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Queensland Children's Hospital /ID# 163146 Recruiting
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Women and Childrens Hospital /ID# 163147 Recruiting
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Royal Children's Hospital /ID# 163104 Recruiting
Melbourne, Victoria, Australia, 3052
Canada, Ontario
Hospital for Sick Children /ID# 163726 Recruiting
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
CHU Sainte-Justine /ID# 163725 Recruiting
Montreal, Quebec, Canada, H3T 1C5
Centre Leon Berard /ID# 163707 Recruiting
Lyon CEDEX 08, Rhone, France, 69373
Hopital de la Timone /ID# 161465 Recruiting
Marseille, France, 13385
Robert Debre Hopital, FR /ID# 161464 Recruiting
Paris, France, 75019
Hopital Armand Trousseau /Id# 163728 Recruiting
Paris, France, 75571
CHU Toulouse - Hôpital des enfants /ID# 163727 Recruiting
Toulouse CEDEX 9, France, 31059
Charite Campus Virchow-Klinikum /ID# 161730 Recruiting
Berlin, Germany, 13353
Universitaetsklinikum Essen /ID# 164207 Recruiting
Essen, Germany, 45147
Universitaetsklinikum Freiburg /ID# 164206 Recruiting
Freiburg, Germany, 79106
Univ Hosp Schleswig-Holstein /ID# 161729 Recruiting
Kiel, Germany, 24105
Erasmus MC - Sophia /ID# 161579 Completed
Rotterdam, Netherlands, 3015 CN
Prinses Maxima Centrum /ID# 162670 Recruiting
Utrecht, Netherlands, 3584 EA
University Children's Hospital /ID# 163037 Recruiting
Zurich, Switzerland, 8032
United Kingdom
Great Ormond St Hospital NHS /ID# 169238 Not yet recruiting
London, United Kingdom, WC1N 3JH
The Newcastle Upon Tyne Hospitals NHS Foundation Trust' /ID# 162938 Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Royal Marsden Hospital /ID# 162937 Not yet recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
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Study Director: AbbVie Inc. AbbVie

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: AbbVie Identifier: NCT03236857     History of Changes
Other Study ID Numbers: M13-833
2017-000439-14 ( EudraCT Number )
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by AbbVie:
relapsed or refractory
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Leukemia, Myeloid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents