Clinical trial NCT03236857: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignancies
Acute Lymphoblastic Leukemia (ALL)
Acute Myeloid Leukemia (AML)
Non-Hodgkin's Lymphoma
Neuroblastoma
Keywords: Cancer
Venetoclax
pediatric
relapsed or refractory
Venclexta
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Roche-Genentech
First posted: 2017-08-02
Enrollment: 143
Sex: ALL
Minimum age (years): 0
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 (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.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: Up to 9 months
measure: Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy
timeFrame: First 21 days venetoclax monotherapy
measure: Recommended Phase 2 dose (RPTD) of Venetoclax
timeFrame: First 21 days venetoclax monotherapy
measure: Cmax of Venetoclax
timeFrame: Up to approximately 2 weeks
measure: Tmax of venetoclax
timeFrame: Up to approximately 2 weeks
measure: AUC0-24 Post-Dose of Venetoclax
timeFrame: Up to approximately 2 weeks
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 9 months
measure: Partial Response (PR) Rate
timeFrame: Up to 9 months
measure: Complete Response (CR) Rate
timeFrame: Up to 9 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Univ California, San Francisco /ID# 163460
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado /ID# 161551
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlan /ID# 161552
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 163440
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 163444
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital /ID# 161550
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia /ID# 163445
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital /ID# 163447
state: Tennessee
city: Salt Lake City
country: United States
facility: Primary Children's /ID# 164399
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital /ID# 163459
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin /ID# 163461
state: Wisconsin
city: Randwick
country: Australia
facility: Sydney Children's Hospital /ID# 163148
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital /ID# 163146
state: Queensland
city: North Adelaide
country: Australia
facility: Women and Childrens Hospital /ID# 163147
state: South Australia
city: Parkville
country: Australia
facility: Royal Children's Hospital /ID# 163104
state: Victoria
city: Toronto
country: Canada
facility: Hospital for Sick Children /ID# 163726
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine /ID# 163725
state: Quebec
city: Marseille CEDEX 05
country: France
facility: AP-HM - Hopital de la Timone /ID# 161465
state: Bouches-du-Rhone
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 163707
state: Rhone
city: Paris
country: France
facility: AP-HP - Hopital Armand-Trousseau /ID# 163728
city: Paris
country: France
facility: Robert Debre Hopital, FR /ID# 161464
city: Toulouse CEDEX 9
country: France
facility: CHU Toulouse - Hôpital des enfants /ID# 163727
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg /ID# 164206
state: Baden-Wuerttemberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161729
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 161730
city: Essen
country: Germany
facility: Universitaetsklinikum Essen /ID# 164207
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia /ID# 161579
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum /ID# 162670
city: Zurich
country: Switzerland
facility: Kinderspital Zurich - Eleonorenstiftung /ID# 163037
state: Zuerich
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children /ID# 169238
state: London, City Of
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 162938
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.