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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. Read our disclaimer for details. Identifier: NCT03236857
Recruitment Status : Completed
First Posted : August 2, 2017
Last Update Posted : May 22, 2023
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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 143 participants
Allocation: N/A
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
Actual Primary Completion Date : April 19, 2023
Actual Study Completion Date : April 19, 2023

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
  • Venclexta

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

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

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

  6. 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.

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   0 Years 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 (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.

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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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    
Other Study ID Numbers: M13-833
2017-000439-14 ( EudraCT Number )
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: May 22, 2023
Last Verified: November 2022
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
Hematologic Diseases
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