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A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

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ClinicalTrials.gov Identifier: NCT03181126
Recruitment Status : Recruiting
First Posted : June 8, 2017
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

June 5, 2017
June 8, 2017
November 12, 2018
November 28, 2017
March 7, 2020   (Final data collection date for primary outcome measure)
  • Cmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Maximum observed plasma concentration (Cmax) 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
  • Tmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Time to Cmax (Tmax) of Venetoclax + Navitoclax
  • CL/F of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
    Apparent oral clearance (CL/F) of venetoclax + navitoclax
  • Number of participants with dose-limiting toxicities (DLT) [ Time Frame: Up to approximately 28 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.
  • 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
Complete list of historical versions of study NCT03181126 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 or Chimeric antigen receptor T-cell (CAR-T) Therapy [ 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 or CAR-T therapy.
  • 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.
  • 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]) for ALL subjects and (CR+PR) for LL subjects.
  • 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.
  • 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.
Not Provided
Not Provided
 
A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
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/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma.
Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Acute Lymphoblastic Leukemia (ALL)
  • Lymphoblastic Lymphoma
  • Drug: Navitoclax
    tablet
    Other Name: ABT-263
  • Drug: Chemotherapy
    peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)
  • Drug: Venetoclax
    tablet
    Other Name: ABT-199 GDC-0199
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 [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
Interventions:
  • Drug: Navitoclax
  • Drug: Chemotherapy
  • Drug: Venetoclax
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
42
Same as current
June 17, 2020
March 7, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.

    • Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
    • Participants with LL must have radiographic evidence of disease
  • 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 central nervous system (CNS) disease with cranial involvement that requires radiation.
  • 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:

    • Inotuzumab within 30 days and must have ALT, AST and bilirubin < ULN.
    • 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

      • Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control disease
    • 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 excluded antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
  • Participants with malabsorption syndrome or any other condition that precludes enteral administration.
Sexes Eligible for Study: All
4 Years and older   (Child, Adult, Older Adult)
No
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Australia,   United States
 
 
NCT03181126
M16-106
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: Undecided
AbbVie
AbbVie
Not Provided
Study Director: AbbVie Inc. AbbVie
AbbVie
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP