Clinical Trials /

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

NCT03236857

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: M13-833
  • SECONDARY ID: 2017-000439-14
  • NCT ID: NCT03236857

Conditions

  • Malignancies
  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myeloid Leukemia (AML)
  • Non-Hodgkin's Lymphoma
  • Neuroblastoma

Interventions

DrugSynonymsArms
chemotherapyVenetoclax with or without chemotherapy
venetoclaxABT-199, GDC-0199Venetoclax with or without chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Venetoclax with or without chemotherapyExperimentalVenetoclax 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.
  • chemotherapy
  • venetoclax

Eligibility 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.
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:AUC0-24 post-dose of venetoclax
Time Frame:Up to approximately 2 weeks
Safety Issue:
Description:Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Cancer
  • Venetoclax
  • pediatric
  • relapsed or refractory

Last Updated

September 25, 2019