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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03236857




Registration number
NCT03236857
Ethics application status
Date submitted
31/07/2017
Date registered
2/08/2017
Date last updated
22/05/2023

Titles & IDs
Public title
A Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
Scientific title
A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients With Relapsed or Refractory Malignancies
Secondary ID [1] 0 0
2017-000439-14
Secondary ID [2] 0 0
M13-833
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignancies 0 0
Acute Lymphoblastic Leukemia (ALL) 0 0
Acute Myeloid Leukemia (AML) 0 0
Non-Hodgkin's Lymphoma 0 0
Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - chemotherapy
Treatment: Drugs - venetoclax

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.


Treatment: Drugs: 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

Treatment: Drugs: venetoclax
Oral tablet for participants; Tablet for oral suspension (participants who cannot swallow a tablet)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Adverse Events
Timepoint [1] 0 0
Up to 9 months
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy
Timepoint [2] 0 0
First 21 days venetoclax monotherapy
Primary outcome [3] 0 0
Recommended Phase 2 dose (RPTD) of Venetoclax
Timepoint [3] 0 0
First 21 days venetoclax monotherapy
Primary outcome [4] 0 0
Cmax of Venetoclax
Timepoint [4] 0 0
Up to approximately 2 weeks
Primary outcome [5] 0 0
Tmax of venetoclax
Timepoint [5] 0 0
Up to approximately 2 weeks
Primary outcome [6] 0 0
AUC0-24 Post-Dose of Venetoclax
Timepoint [6] 0 0
Up to approximately 2 weeks
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to 9 months
Secondary outcome [2] 0 0
Partial Response (PR) Rate
Timepoint [2] 0 0
Up to 9 months
Secondary outcome [3] 0 0
Complete Response (CR) Rate
Timepoint [3] 0 0
Up to 9 months

Eligibility
Key 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).
Minimum age
0 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/04/2023
Sample size
Target
Accrual to date
Final
143
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital /ID# 163148 - Randwick
Recruitment hospital [2] 0 0
Queensland Children's Hospital /ID# 163146 - South Brisbane
Recruitment hospital [3] 0 0
Women and Childrens Hospital /ID# 163147 - North Adelaide
Recruitment hospital [4] 0 0
Royal Children's Hospital /ID# 163104 - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Bouches-du-Rhone
Country [15] 0 0
France
State/province [15] 0 0
Rhone
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Toulouse CEDEX 9
Country [18] 0 0
Germany
State/province [18] 0 0
Baden-Wuerttemberg
Country [19] 0 0
Germany
State/province [19] 0 0
Schleswig-Holstein
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Essen
Country [22] 0 0
Netherlands
State/province [22] 0 0
Rotterdam
Country [23] 0 0
Netherlands
State/province [23] 0 0
Utrecht
Country [24] 0 0
Switzerland
State/province [24] 0 0
Zuerich
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London, City Of
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Roche-Genentech
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03236857
Trial related presentations / publications
Dalton KM, Krytska K, Lochmann TL, Sano R, Casey C, D'Aulerio A, Khan QA, Crowther GS, Coon C, Cai J, Jacob S, Kurupi R, Hu B, Dozmorov M, Greninger P, Souers AJ, Benes CH, Mosse YP, Faber AC. Venetoclax-based Rational Combinations are Effective in Models of MYCN-amplified Neuroblastoma. Mol Cancer Ther. 2021 Aug;20(8):1400-1411. doi: 10.1158/1535-7163.MCT-20-0710. Epub 2021 Jun 4.
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.
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03236857