Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02203773
Recruitment Status : Active, not recruiting
First Posted : July 30, 2014
Last Update Posted : December 22, 2020
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE July 10, 2014
First Posted Date  ICMJE July 30, 2014
Last Update Posted Date December 22, 2020
Actual Study Start Date  ICMJE October 6, 2014
Estimated Primary Completion Date September 27, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
  • Complete Remission Rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
  • The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
  • Complete Remission with incomplete blood count recovery rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Complete Remission with incomplete blood count recovery Rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.
  • half-life (t1/2) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time required for the concentration of the drug to reach half of its original value.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Maximum observed concentration, occurring at Tmax.
  • Overall Response Rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission(PR) per the International Working Group criteria for AML.
  • Clearance (CL) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Clearance is defined as the rate at which drug is cleared from the blood.
  • AUC from 0-24 (AUC0-24) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
  • Time to Cmax (peak time, Tmax), [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time at which maximum plasma concentration (Cmax) is observed.
  • AUC from 0 to infinity (AUC∞) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Area under the plasma concentration-versus-time curve from time zero to infinity.
  • Overall Survival [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Overall survival will be defined as the number of days from the date of enrollment to the date of death.
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2014)
  • Adverse Event (AE) monitoring of ABT-199 in combination with decitabine and azacitidine [ Time Frame: Measured from Day 1 up to 2 years after the last subject has enrolled ]
    AE monitoring will be assessed by evaluation of study drug exposure, AEs , serious AEs, all deaths, as well as laboratory determinations and vital sign parameters.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Maximum observed concentration, occurring at Tmax.
  • The time to Cmax (peak time, Tmax), [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time at which maximum plasma concentration (Cmax) is observed.
  • The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
  • AUC from 0-24 (AUC0-24) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
  • half-life (t1/2) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time required for the concentration of the drug to reach half of its original value.
  • AUC from 0 to infinity (AUC∞) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Area under the plasma concentration-versus-time curve from time zero to infinity.
  • Clearance (CL) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Clearance is defined as the rate at which drug is cleared from the blood.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
  • Percent of subjects who move on to stem cell transplant [ Time Frame: Measured up to 1 year after the last subject last dose ]
    The percent of subjects who move on to stem cell transplant will be summarized.
  • Duration of Response [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).
  • Event Free Survival [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Event-free survival (EFS) will be defined as the number of days from the date of first dose to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete response (CR + CRi), or death.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2014)
  • Overall response rate [ Time Frame: Measured up to 2 years after the last subject has enrolled. ]
    Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission(PR) per the International Working Group criteria for AML.
  • Duration of Response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).
  • Time to Progression [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Time to progression will be defined as the number of days from the date of enrollment to the date of earliest disease progression.
  • Progression-Free Survival [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Time to progression will be defined as the number of days from the date of enrollment to the date of earliest disease progression or death.
  • Overall Survival [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Overall survival will be defined as the number of days from the date of enrollment to the date of death.
  • Minimal Residual Disease (MRD) Negativity Rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    The presence of less than one AML cell per 10,000 leukocytes in either peripheral blood and/or bone marrow.
  • Changes in clinical laboratory test results [ Time Frame: Measured from Day 1 up to 2 years after the last subject has enrolled in the study. ]
    chemistry, hematology, and urinalysis
  • Changes in physical exam findings, including vital signs. [ Time Frame: Measured from Day 1 up to 2 years after the last subject has enrolled in the study. ]
    Body temperature, weight, blood pressure, heart rate, and respiratory rate
  • Percent of subjects who move on to stem cell transplant [ Time Frame: Measure up to 2 years after the last subject has enrolled in the study. ]
    The percent of subjects who move on to stem cell transplant will be summarized.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
Official Title  ICMJE A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
Brief Summary This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered ABT-199 combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of ABT-199 in combination with posaconazole.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myelogenous Leukemia
  • Myelogenous Leukemia
  • Treatment Naive AML
Intervention  ICMJE
  • Drug: Posaconazole
    Posaconazole will be administered orally twice a day on Cycle 1 Day 21 and once daily from Cycle 1 Day 22 to Cycle 1 Day 28.
  • Drug: ABT-199
    ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.
  • Drug: Decitabine
    Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles
  • Drug: Azacitidine
    Azacitidine will be administered by IV infusion over 10 to 40 minutes or subcutaneously based on the institutional guidelines, beginning on Day 1 through Day 7 of each Cycle, for a minimum of 4 Cycles.
Study Arms  ICMJE
  • Experimental: ABT-199 + Azacitidine
    Treatment Naive Acute Myelogenous Leukemia
    Interventions:
    • Drug: ABT-199
    • Drug: Azacitidine
  • Experimental: ABT-199 + Decitabine
    Treatment Naive Acute Myelogenous Leukemia
    Interventions:
    • Drug: ABT-199
    • Drug: Decitabine
  • Experimental: ABT-199+Decitabine+Posaconazole
    Treatment Naive Acute Myelogenous Leukemia
    Interventions:
    • Drug: Posaconazole
    • Drug: ABT-199
    • Drug: Decitabine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 18, 2020)
260
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2014)
89
Estimated Study Completion Date  ICMJE September 27, 2021
Estimated Primary Completion Date September 27, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
  • Subject must have received no prior treatment for AML with the exception of hydroxyurea
  • Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ) to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
  • Subject must have adequate kidney and liver function as described in the protocol

Exclusion Criteria:

  • Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
  • Subject has history of Myeloproliferative Neoplasm (MPN).
  • Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
  • Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
  • Subject has acute promyelocytic leukemia.
  • Subject has known active central nervous system involvement with AML.
  • Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.
  • Subject has a history of other malignancies .prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02203773
Other Study ID Numbers  ICMJE M14-358
2014-000687-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date December 2020

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