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

NCT ID: NCT03236857

Last Updated: 2023-05-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-08

Study Completion Date

2023-04-19

Brief Summary

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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.

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Detailed Description

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Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

chemotherapy

Intervention Type DRUG

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

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

venetoclax

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

Intervention Type DRUG

Other Intervention Names

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ABT-199 GDC-0199 Venclexta

Eligibility Criteria

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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.
Minimum Eligible Age

0 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roche-Genentech

INDUSTRY

Sponsor Role collaborator

AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Univ California, San Francisco /ID# 163460

San Francisco, California, United States

Site Status

Children's Hospital Colorado /ID# 161551

Aurora, Colorado, United States

Site Status

Children's Healthcare of Atlan /ID# 161552

Atlanta, Georgia, United States

Site Status

Dana-Farber Cancer Institute /ID# 163440

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 163444

New York, New York, United States

Site Status

Cincinnati Children's Hospital /ID# 161550

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia /ID# 163445

Philadelphia, Pennsylvania, United States

Site Status

St Jude Children's Research Hospital /ID# 163447

Memphis, Tennessee, United States

Site Status

Primary Children's /ID# 164399

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital /ID# 163459

Seattle, Washington, United States

Site Status

Medical College of Wisconsin /ID# 163461

Milwaukee, Wisconsin, United States

Site Status

Sydney Children's Hospital /ID# 163148

Randwick, New South Wales, Australia

Site Status

Queensland Children's Hospital /ID# 163146

South Brisbane, Queensland, Australia

Site Status

Women and Childrens Hospital /ID# 163147

North Adelaide, South Australia, Australia

Site Status

Royal Children's Hospital /ID# 163104

Parkville, Victoria, Australia

Site Status

Hospital for Sick Children /ID# 163726

Toronto, Ontario, Canada

Site Status

CHU Sainte-Justine /ID# 163725

Montreal, Quebec, Canada

Site Status

AP-HM - Hopital de la Timone /ID# 161465

Marseille, Bouches-du-Rhone, France

Site Status

Centre Leon Berard /ID# 163707

Lyon, Rhone, France

Site Status

AP-HP - Hopital Armand-Trousseau /ID# 163728

Paris, , France

Site Status

Robert Debre Hopital, FR /ID# 161464

Paris, , France

Site Status

CHU Toulouse - Hôpital des enfants /ID# 163727

Toulouse, , France

Site Status

Universitaetsklinikum Freiburg /ID# 164206

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161729

Kiel, Schleswig-Holstein, Germany

Site Status

Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 161730

Berlin, , Germany

Site Status

Universitaetsklinikum Essen /ID# 164207

Essen, , Germany

Site Status

Erasmus MC - Sophia /ID# 161579

Rotterdam, , Netherlands

Site Status

Prinses Maxima Centrum /ID# 162670

Utrecht, , Netherlands

Site Status

Kinderspital Zurich - Eleonorenstiftung /ID# 163037

Zurich, Canton of Zurich, Switzerland

Site Status

Great Ormond Street Hospital for Children /ID# 169238

London, London, City of, United Kingdom

Site Status

The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 162938

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Netherlands Switzerland United Kingdom

References

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Karol SE, Khaw SL, Zwaan CM, Baruchel A, Bittencourt H, Cooper TM, Flotho C, Fraser C, Forlenza CJ, Goldsmith KC, Macy ME, Morgenstern DA, O'Brien MM, Petit A, Ziegler DS, Reinhardt D, Opferman JT, Rubnitz JE, Onishi M, Dunshee DR, Dunbar F, Vishwamitra D, Ross JA, Chen X, Unnebrink K, Kammerlander M, Salem AH, Palenski TL, Sunkersett G, Place AE. Venetoclax Alone or in Combination With Chemotherapy in Paediatric and Adolescent/Young Adult Patients With Relapsed/Refractory Acute Myeloid Leukaemia. Pediatr Blood Cancer. 2025 Jul;72(7):e31714. doi: 10.1002/pbc.31714. Epub 2025 Apr 23.

Reference Type DERIVED
PMID: 40266036 (View on PubMed)

Place AE, Karol SE, Forlenza CJ, Cooper TM, Fraser C, Cario G, O'Brien MM, Gerber NU, Bourquin JP, Reinhardt D, Rubnitz JE, Opferman JT, Sunkersett G, Onishi M, Dunshee DR, Chen X, Unnebrink K, Vishwamitra D, Dunbar F, Badawi M, Ross JA, Loh ML. Venetoclax Combined With Chemotherapy in Pediatric and Adolescent/Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2025 Jun;72(6):e31630. doi: 10.1002/pbc.31630. Epub 2025 Mar 10.

Reference Type DERIVED
PMID: 40062648 (View on PubMed)

Badawi M, Gopalakrishnan S, Engelhardt B, Palenski T, Karol SE, Rubnitz JE, Menon R, Salem AH. Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships. Clin Ther. 2024 Oct;46(10):759-767. doi: 10.1016/j.clinthera.2024.09.008. Epub 2024 Oct 5.

Reference Type DERIVED
PMID: 39368878 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34088831 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29595064 (View on PubMed)

Other Identifiers

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2017-000439-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-833

Identifier Type: -

Identifier Source: org_study_id

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