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A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed Acute Lymphoblastic Leukemia

This study is not yet open for participant recruitment.
Verified October 2017 by AbbVie
Sponsor:
ClinicalTrials.gov Identifier:
NCT03181126
First Posted: June 8, 2017
Last Update Posted: November 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
AbbVie
  Purpose
This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed acute lymphoblastic leukemia.

Condition Intervention Phase
Acute Lymphoblastic Leukemia Drug: Venetoclax Drug: Navitoclax Drug: Chemotherapy Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Number of participants with dose-limiting toxicities (DLT) [ Time Frame: Up to approximately 42 days after initial dose of study drug ]
    A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.

  • Cmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax

  • Tmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Time to Cmax (Tmax) of Venetoclax + Navitoclax

  • AUC of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax

  • CL/F of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Apparent oral clearance (CL/F) of venetoclax + navitoclax


Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    The proportion of subjects with objective response rate (complete response [CR] + CR incomplete recovery [CRi] + CR without platelet recovery [CRp]).

  • Overall survival (OS) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    OS is defined as the number of days from the date of enrollment to the date of death.

  • Progression-free survival (PFS) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    PFS is defined as the number of days from the date of enrollment to the date of earliest disease progression or death.

  • Complete Response (CR) rate [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    CR defined as hematologic recovery (absolute neutrophil count [ANC] greater than or equal to 500/μL; platelet counts greater than or equal to 75,000/μL), evidence of trilineage hematopoiesis in the bone marrow and less than 5% blasts in the bone marrow, absence of circulating blasts, and no evidence of extramedullary disease.

  • Partial Response (PR) rate [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    PR defined as no peripheral blasts or peripheral blood absolute blast count decreased by ≥ 50% from baseline, bone marrow with 5 - 25% blasts and at least a 50% decrease in bone marrow blast percent from baseline, no evidence of extramedullary disease.

  • Number of Participant who Proceed to Stem Cell Transplantation [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]
    Determine the number of participants who proceed to stem cell transplantation.


Estimated Enrollment: 42
Anticipated Study Start Date: November 30, 2017
Estimated Study Completion Date: June 12, 2020
Estimated Primary Completion Date: March 7, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase + vincristine + dexamethasone) starting on Day 9 (chemotherapy may be delayed, or not administered, at the discretion of the investigator)
Drug: Venetoclax
tablet
Other Names:
  • ABT-199
  • GDC-0199
Drug: Navitoclax
tablet
Other Name: ABT-263
Drug: Chemotherapy
peg-asparaginase (intravenous) + vincristine (intravenous) + dexamethasone (oral)

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have relapsed or refractory acute lymphoblastic leukemia (ALL).
  • Must weigh greater than or equal to 20 kg.
  • Must be able to swallow pills.
  • Must have adequate hepatic and kidney function.
  • Must have adequate performance status:

    • Participants less than or equal to 16 years of age: Lansky greater than or equal to 50
    • Participants greater than 16 years of age: Karnofsky greater than or equal to 50 or Eastern Cooperative Oncology Group (ECOG) less than 3.

Exclusion Criteria:

  • Participant has overt central nervous system (CNS) disease (CNS 3 status)
  • Participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug.
  • Participants who have received any of the following prior to the first dose of study drug:

    • A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days
    • CAR-T infusion or other cellular therapy within 30 days
    • any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter
    • Steroid therapy for anti-neoplastic intent within 5 days
    • Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
    • A strong or moderate CYP3A inhibitor or inducer within 7 days
    • Aspirin within 7 days, or 5 half-lives, whichever is longer
    • An antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
    • A CYP2C8 or CYP2C9 substrate within 7 days, or 5 half-lives, whichever is longer
  • Participants with malabsorption syndrome or any other condition that precludes enteral administration.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03181126


Contacts
Contact: AbbVie_Call Center 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
United States, California
LPCH Stanford /ID# 163337 Not yet recruiting
Palo Alto, California, United States, 94304
United States, Illinois
University of Chicago /ID# 163369 Recruiting
Chicago, Illinois, United States, 60637
United States, Missouri
Washington University School of Medicine /ID# 165689 Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
University of North Carolina at Chapel Hill /ID# 163509 Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital /ID# 164619 Not yet recruiting
Cincinnati, Ohio, United States, 45229
Nationwide Childrens Hospital /ID# 163372 Not yet recruiting
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health & Science University (OHSU) /ID# 165690 Not yet recruiting
Portland, Oregon, United States, 97239
United States, Tennessee
St. Jude Childrens Research Hospital /ID# 163335 Not yet recruiting
Memphis, Tennessee, United States, 38105
United States, Texas
UT Southwestern Medical Center /ID# 163346 Not yet recruiting
Dallas, Texas, United States, 75390-9063
MD Anderson Cancer Center /ID# 163327 Not yet recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin-Madison /ID# 165691 Not yet recruiting
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc AbbVie
  More Information

Additional Information:
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03181126     History of Changes
Other Study ID Numbers: M16-106
First Submitted: June 5, 2017
First Posted: June 8, 2017
Last Update Posted: November 1, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AbbVie:
Relapsed of Refractory Acute Lymphoblastic Leukemia
Navitoclax
Cancer
Venetoclax

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Venetoclax
Navitoclax
Antineoplastic Agents