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

Neuroblastoma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03236857
• Other study ID #: M13-833
• Secondary ID: 2017-000439-14
• Status: Completed
• Phase: Phase 1
• Start date: November 8, 2017
• Est. completion date: April 19, 2023

Study information

• Verified date: November 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: April 19, 2023
• Est. primary completion date: April 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 25 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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
• venetoclax
Oral tablet for participants; Tablet for oral suspension (participants who cannot swallow a tablet)

Locations

Country	Name	City	State
Australia	Women and Childrens Hospital /ID# 163147	North Adelaide	South Australia
Australia	Royal Children's Hospital /ID# 163104	Parkville	Victoria
Australia	Sydney Children's Hospital /ID# 163148	Randwick	New South Wales
Australia	Queensland Children's Hospital /ID# 163146	South Brisbane	Queensland
Canada	CHU Sainte-Justine /ID# 163725	Montreal	Quebec
Canada	Hospital for Sick Children /ID# 163726	Toronto	Ontario
France	Centre Leon Berard /ID# 163707	Lyon CEDEX 08	Rhone
France	AP-HM - Hopital de la Timone /ID# 161465	Marseille CEDEX 05	Bouches-du-Rhone
France	AP-HP - Hopital Armand-Trousseau /ID# 163728	Paris
France	Robert Debre Hopital, FR /ID# 161464	Paris
France	CHU Toulouse - Hôpital des enfants /ID# 163727	Toulouse CEDEX 9
Germany	Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 161730	Berlin
Germany	Universitaetsklinikum Essen /ID# 164207	Essen
Germany	Universitaetsklinikum Freiburg /ID# 164206	Freiburg	Baden-Wuerttemberg
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161729	Kiel	Schleswig-Holstein
Netherlands	Erasmus MC - Sophia /ID# 161579	Rotterdam
Netherlands	Prinses Maxima Centrum /ID# 162670	Utrecht
Switzerland	Kinderspital Zurich - Eleonorenstiftung /ID# 163037	Zurich	Zuerich
United Kingdom	Great Ormond Street Hospital for Children /ID# 169238	London	London, City Of
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 162938	Newcastle Upon Tyne
United States	Children's Healthcare of Atlan /ID# 161552	Atlanta	Georgia
United States	Children's Hospital Colorado /ID# 161551	Aurora	Colorado
United States	Dana-Farber Cancer Institute /ID# 163440	Boston	Massachusetts
United States	Cincinnati Children's Hospital /ID# 161550	Cincinnati	Ohio
United States	St Jude Children's Research Hospital /ID# 163447	Memphis	Tennessee
United States	Medical College of Wisconsin /ID# 163461	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 163444	New York	New York
United States	Children's Hospital of Philadelphia /ID# 163445	Philadelphia	Pennsylvania
United States	Primary Children's /ID# 164399	Salt Lake City	Utah
United States	Univ California, San Francisco /ID# 163460	San Francisco	California
United States	Seattle Children's Hospital /ID# 163459	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Roche-Genentech

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Adverse Events	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.	Up to 9 months
Primary	Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy	A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol.	First 21 days venetoclax monotherapy
Primary	Recommended Phase 2 dose (RPTD) of Venetoclax	Venetoclax RPTD is the dose determined based on adverse event reporting and dose-limiting toxicity information from all participants.	First 21 days venetoclax monotherapy
Primary	Cmax of Venetoclax	Maximum plasma concentration (Cmax) of venetoclax.	Up to approximately 2 weeks
Primary	Tmax of venetoclax	Time to maximum plasma concentration (Tmax) of venetoclax.	Up to approximately 2 weeks
Primary	AUC0-24 Post-Dose of Venetoclax	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.	Up to approximately 2 weeks
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who achieved a response according to established criteria described in detail in the study protocol.	Up to 9 months
Secondary	Partial Response (PR) Rate	PR is defined according to established criteria for each tumor type and is described in detail within the study protocol.	Up to 9 months
Secondary	Complete Response (CR) Rate	CR is defined according to established criteria for each tumor type and is described in detail within the study protocol.	Up to 9 months