A Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
- Conditions
- MalignanciesAcute Lymphoblastic Leukemia (ALL)Acute Myeloid Leukemia (AML)Non-Hodgkin's LymphomaNeuroblastoma
- Interventions
- Drug: chemotherapy
- Registration Number
- NCT03236857
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- 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).
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Participants with primary brain tumors or disease metastatic to the brain.
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Participants who have central nervous system (CNS) disease with cranial involvement that requires radiation.
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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)
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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.
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Participants who are less than 6 weeks post-131 I-metaiodobenzylguanidine (mIBG) therapy.
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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).
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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).
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Participants who have active, uncontrolled infections.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Venetoclax with or without chemotherapy 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. Venetoclax with or without chemotherapy venetoclax 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.
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events 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.
Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy 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 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 Up to approximately 2 weeks Maximum plasma concentration (Cmax) of venetoclax.
Tmax of venetoclax Up to approximately 2 weeks Time to maximum plasma concentration (Tmax) of venetoclax.
AUC0-24 Post-Dose of Venetoclax 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
Name Time Method Partial Response (PR) Rate Up to 9 months PR is defined according to established criteria for each tumor type and is described in detail within the study protocol.
Objective Response Rate (ORR) 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 Up to 9 months CR is defined according to established criteria for each tumor type and is described in detail within the study protocol.
Trial Locations
- Locations (31)
AP-HM - Hopital de la Timone /ID# 161465
🇫🇷Marseille CEDEX 05, Bouches-du-Rhone, France
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 163444
🇺🇸New York, New York, United States
Robert Debre Hopital, FR /ID# 161464
🇫🇷Paris, France
St Jude Children's Research Hospital /ID# 163447
🇺🇸Memphis, Tennessee, United States
Sydney Children's Hospital /ID# 163148
🇦🇺Randwick, New South Wales, Australia
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 161730
🇩🇪Berlin, Germany
Primary Children's /ID# 164399
🇺🇸Salt Lake City, Utah, United States
Children's Healthcare of Atlan /ID# 161552
🇺🇸Atlanta, Georgia, United States
Dana-Farber Cancer Institute /ID# 163440
🇺🇸Boston, Massachusetts, United States
Cincinnati Children's Hospital /ID# 161550
🇺🇸Cincinnati, Ohio, United States
Seattle Children's Hospital /ID# 163459
🇺🇸Seattle, Washington, United States
Children's Hospital of Philadelphia /ID# 163445
🇺🇸Philadelphia, Pennsylvania, United States
Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161729
🇩🇪Kiel, Schleswig-Holstein, Germany
Children's Hospital Colorado /ID# 161551
🇺🇸Aurora, Colorado, United States
Univ California, San Francisco /ID# 163460
🇺🇸San Francisco, California, United States
Royal Children's Hospital /ID# 163104
🇦🇺Parkville, Victoria, Australia
Medical College of Wisconsin /ID# 163461
🇺🇸Milwaukee, Wisconsin, United States
Queensland Children's Hospital /ID# 163146
🇦🇺South Brisbane, Queensland, Australia
CHU Sainte-Justine /ID# 163725
🇨🇦Montreal, Quebec, Canada
Centre Leon Berard /ID# 163707
🇫🇷Lyon CEDEX 08, Rhone, France
AP-HP - Hopital Armand-Trousseau /ID# 163728
🇫🇷Paris, France
CHU Toulouse - Hôpital des enfants /ID# 163727
🇫🇷Toulouse CEDEX 9, France
Universitaetsklinikum Essen /ID# 164207
🇩🇪Essen, Germany
Erasmus MC - Sophia /ID# 161579
🇳🇱Rotterdam, Netherlands
Great Ormond Street Hospital for Children /ID# 169238
🇬🇧London, London, City Of, United Kingdom
Prinses Maxima Centrum /ID# 162670
🇳🇱Utrecht, Netherlands
Kinderspital Zurich - Eleonorenstiftung /ID# 163037
🇨ðŸ‡Zurich, Zuerich, Switzerland
Universitaetsklinikum Freiburg /ID# 164206
🇩🇪Freiburg, Baden-Wuerttemberg, Germany
Women and Childrens Hospital /ID# 163147
🇦🇺North Adelaide, South Australia, Australia
Hospital for Sick Children /ID# 163726
🇨🇦Toronto, Ontario, Canada
The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 162938
🇬🇧Newcastle Upon Tyne, United Kingdom