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

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ClinicalTrials.gov Identifier: NCT03236857
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
AbbVie

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
Criteria

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 ClinicalTrials.gov identifier (NCT number): NCT03236857


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

  Show 33 Study Locations
Sponsors and Collaborators
AbbVie
Roche-Genentech
Investigators
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Study Director: AbbVie Inc. AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov 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: July 10, 2019
Last Verified: July 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:
Cancer
Venetoclax
pediatric
relapsed or refractory
Additional relevant MeSH terms:
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Venetoclax
Leukemia
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neuroblastoma
Neoplasms
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