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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 : September 26, 2019
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE July 31, 2017
First Posted Date  ICMJE August 2, 2017
Last Update Posted Date September 26, 2019
Actual Study Start Date  ICMJE November 8, 2017
Estimated Primary Completion Date April 7, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • 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
  • 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.
  • 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.
  • Tmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Time to maximum plasma concentration (Tmax) of venetoclax
  • Cmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Maximum plasma concentration (Cmax) of venetoclax
Original Primary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
  • 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.
  • 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.
  • Cmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Maximum plasma concentration (Cmax) of venetoclax
  • Tmax of venetoclax [ Time Frame: Up to approximately 2 weeks ]
    Time to maximum plasma concentration (Tmax) of venetoclax
  • 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
Change History Complete list of historical versions of study NCT03236857 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
Official Title  ICMJE A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignancies
  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myeloid Leukemia (AML)
  • Non-Hodgkin's Lymphoma
  • Neuroblastoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: chemotherapy
  • Drug: venetoclax
Publications * Place AE, Goldsmith K, Bourquin JP, Loh ML, Gore L, Morgenstern DA, Sanzgiri Y, Hoffman D, Zhou Y, Ross JA, Prine B, Shebley M, McNamee M, Farazi T, Kim SY, Verdugo M, Lash-Fleming L, Zwaan CM, Vormoor J. Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies. Future Oncol. 2018 Sep;14(21):2115-2129. doi: 10.2217/fon-2018-0121. Epub 2018 Mar 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2018)
165
Original Estimated Enrollment  ICMJE
 (submitted: July 31, 2017)
135
Estimated Study Completion Date  ICMJE April 7, 2022
Estimated Primary Completion Date April 7, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Germany,   Netherlands,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03236857
Other Study ID Numbers  ICMJE M13-833
2017-000439-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Roche-Genentech
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP