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Trial record 1 of 1 for:    NCT02993523
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A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

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: NCT02993523
Recruitment Status : Active, not recruiting
First Posted : December 15, 2016
Last Update Posted : February 28, 2020
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE December 13, 2016
First Posted Date  ICMJE December 15, 2016
Last Update Posted Date February 28, 2020
Actual Study Start Date  ICMJE February 2, 2017
Estimated Primary Completion Date May 23, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2019)
  • Overall survival (OS) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    OS is defined as the number of days from the date of randomization to the date of death.
  • Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/ microliter (mcL), platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
  • Proportion of participants with complete remission (CR) or complete remission with incomplete marrow recovery (CRi) [ Time Frame: Up to 6 months after the first 225 subjects are randomized ]
    This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/ microliter (mcL), platelets >= 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of < 10^3/mcL or platelets < 10^5/mcL.
  • Overall survival (OS) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    OS is defined as the number of days from the date of randomization to the date of death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2019)
  • Event-free survival (EFS) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.
  • Global health status/quality of life (GHS/QoL) [ Time Frame: Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit ]
    Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
  • Percentage of participants achieving composite complete remission (CR or CRi) [ Time Frame: Up to 6 months after the first 225 participants are randomized ]
    This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.
  • Complete remission or complete remission with partial hematologic recovery rate (CR+CRh) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    A response of CRh is defined as Bone marrow with <5% blasts, peripheral blood neutrophil count >0.5*10^3/mcL and peripheral blood platelet count >0.5*10^5/mcL.
  • Post baseline transfusion independence rate [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.
  • Complete remission (CR) rate [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.
  • Fatigue/quality of life (QoL) [ Time Frame: Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit ]
    Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and Cancer Fatigue Short Form (SF) 7a global fatigue score
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
  • Change in time to first composite complete remission (CR or CRi) [ Time Frame: Up to 6 months after the first 225 subjects are randomized ]
    This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets >= 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of < 10^3/mcL or platelets < 10^5/mcL.
  • Event-free survival (EFS) [ Time Frame: Measured up to 2 years after the last participant is randomized ]
    EFS will be defined as the number of days from the date of randomization to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.
  • Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a [ Time Frame: Measured at participant's Day 1 of Cycle 1 and at Day 1 of every Cycle thereafter for up to 3 years following the last subject last visit ]
    Fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form [SF] 7a global fatigue score. PROMIS Cancer Fatigue SF 7a is a seven item questionnaire that assesses the impact and experience of fatigue over the past 7 days.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy
Official Title  ICMJE A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy
Brief Summary

Acute Myeloid Leukaemia (AML) is an aggressive and rare cancer of myeloid cells (a white blood cell responsible for fighting infections). Successful treatment of AML is dependent on what subtype of AML the participant has, and the age of the participant when diagnosed.

Venetoclax is an experimental drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. This study is designed to see if adding venetoclax to azacitidine works better than azacitidine on its own.

This is a Phase 3, randomized, double-blind (treatment is unknown to participants and doctors), placebo controlled study in patients with AML who are >= 18 or more years old and have not been treated before. Participants who take part in this study should not be suitable for standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 180 hospitals globally and enroll approximately 400 participants.

In this study, 2/3 of participants will receive venetoclax every day with azacitidine and the remaining 1/3 will receive placebo (dummy) tablets with azacitidine.

Participants will continue to have study visits and receive treatment for as long as they are having a clinical benefit. The effect of the treatment on AML will be checked by taking blood, bone marrow, scans, measuring side effects and by completing health questionnaires. Blood and bone marrow tests will be completed to see why some people respond better than others. Additional blood tests will be completed for genetic factors and to see how long the drug remains in the body.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Azacitidine
    Solution for subcutaneous or intravenous administration
  • Drug: Venetoclax
    Tablet
    Other Name: ABT-199
  • Drug: Placebo
    Tablet
Study Arms  ICMJE
  • Placebo Comparator: Placebo followed by Azacitidine
    Matching Placebo for Venetoclax 400 mg orally QD on Days 1 - 28 plus Azacitidine 75 mg/m^2 SC or IV QD on Days 1 - 7 (28-day cycle)
    Interventions:
    • Drug: Azacitidine
    • Drug: Placebo
  • Active Comparator: Venetoclax followed by Azacitidine
    Venetoclax 400 mg orally every day (QD) on Days 1 - 28 plus Azacitidine 75 mg/m^2 subcutaneously (SC) or intravenous (IV) QD on Cycle Days 1 - 7 (28-day cycle)
    Interventions:
    • Drug: Azacitidine
    • Drug: Venetoclax
Publications * Not Provided

*   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
Actual Enrollment  ICMJE
 (submitted: June 12, 2019)
443
Original Estimated Enrollment  ICMJE
 (submitted: December 13, 2016)
400
Estimated Study Completion Date  ICMJE May 23, 2021
Estimated Primary Completion Date May 23, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
  • Participant must be >= 18 years of age.
  • Participant must have a projected life expectancy of at least 12 weeks.
  • Participant must be considered ineligible for induction therapy defined by the following:

    a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v. Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); vi. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie Therapeutic Medical Director during screening and before study enrollment.

  • Participant must have an ECOG Performance status:

    1. 0 to 2 for Participants >= 75 years of age or
    2. 0 to 3 for Participants >= 18 to 74 years of age.
  • Participant must have adequate renal function as demonstrated by a creatinine >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
  • Participant must have adequate liver function as demonstrated by:

    1. aspartate aminotransferase (AST) <= 3.0 x ULN*
    2. alanine aminotransferase (ALT) <= 3.0 x ULN*
    3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement

    i. Subjects who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

  • Female participants must be either postmenopausal defined as:

    1. Age > 55 years with no menses for 12 or more months without an alternative medical cause.
    2. Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L; or
    3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or
    4. Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
  • Male Participants who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
  • Female participants of childbearing potential must have negative results for pregnancy test performed:

    1. At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
    2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.
  • Participant must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  • Participant has received treatment with the following:

    1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
    2. Chimeric Antigen Receptor (CAR)-T cell therapy.
    3. Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
    4. Current participation in another research or observational study.
  • Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
  • Participant has the following:

    a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia.

  • Participant has acute promyelocytic leukemia
  • Participant has known active central nervous system (CNS) involvement with AML.
  • Participant has known HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax) HIV testing will be performed at Screening, only if required per local guidelines or institutional standards.
  • Participant is known to be positive for hepatitis B or C infection [HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on HBV DNA PCR test for HBc Ab and/or HBs Ab positivity] with the exception of those with an undetectable viral load within 3 months screening. Hepatitis B or C testing is not required.
  • Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment; additional details as described in the protocol.
  • Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
  • Participant has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
  • Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
  • Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
  • Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
  • Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:

    1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
    2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    3. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.
  • Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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,   Austria,   Belgium,   Brazil,   Canada,   China,   Croatia,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Norway,   Poland,   Portugal,   Puerto Rico,   Russian Federation,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02993523
Other Study ID Numbers  ICMJE M15-656
2016-001466-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
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)
Supporting Materials: Analytic Code
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 February 2020

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