Clinical Trials /

A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

NCT03069352

Description:

The primary objective of this study is to evaluate if venetoclax when co administered with low-dose cytarabine (LDAC) improves overall survival (OS) versus LDAC and placebo, in treatment-naïve patients with acute myeloid leukemia (AML).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
  • Official Title: A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax Co-Administered With Low Dose Cytarabine Versus Low Dose Cytarabine in Treatment Naïve Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: M16-043
  • SECONDARY ID: 2016-003900-30
  • NCT ID: NCT03069352

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
PlaceboPlacebo + LDAC
VenetoclaxABT-199, VenclextaVenetoclax + Low Dose Cytarabine (LDAC)
CytarabineCytosar-U, Ara-C, ArabinosylcytosinePlacebo + LDAC

Purpose

The primary objective of this study is to evaluate if venetoclax when co administered with low-dose cytarabine (LDAC) improves overall survival (OS) versus LDAC and placebo, in treatment-naïve patients with acute myeloid leukemia (AML).

Detailed Description

      Acute myeloid leukemia (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 patient has, and the age of the patient 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 cytarabine works better than cytarabine on its own.

      This is a Phase 3, randomized, double-blind (treatment unknown to patients and doctors),
      placebo-controlled, multicenter study in patients with AML who are 18 or more years old and
      have not been treated before. Patients who take part in this study should not be suitable for
      intensive induction chemotherapy (usual starting treatment). Abbvie is funding this study
      which will take place at approximately 125 hospitals globally. In this study, 2/3 of patients
      will receive venetoclax every day with cytarabine and the remaining 1/3 will receive placebo
      (dummy) tablets with cytarabine.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Venetoclax + Low Dose Cytarabine (LDAC)ExperimentalVenetoclax 600 mg orally every day (QD) plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
  • Venetoclax
  • Cytarabine
Placebo + LDACPlacebo ComparatorMatching placebo to venetoclax orally QD plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
  • Placebo
  • Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          1. Participant must have histological confirmation of acute myeloid leukemia (AML) by
             World Health Organization criteria, be ineligible for intensive induction chemotherapy
             and either be:

               -  ≥ 75 years of age OR

               -  ≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of
                  fitness for intensive induction chemotherapy:

                    -  Eastern Cooperative Oncology Group (ECOG) performance status of 2 - 3

                    -  Cardiac history of congestive heart failure (CHF) requiring treatment or
                       ejection fraction ≤ 50% or chronic stable angina

                    -  Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced
                       expiratory volume in 1 second (FEV1) ≤ 65%

                    -  Creatinine clearance ≥ 30 mL/min to < 45 ml/min

                    -  Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × upper
                       limit of normal (ULN)

                    -  Other comorbidity that the physician judges to be incompatible with
                       conventional intensive chemotherapy which must be reviewed and approved by
                       the study medical monitor before study enrollment

          2. Participant must have an ECOG performance status:

               -  of 0 to 2 for subjects ≥ 75 years of age OR

               -  of 0 to 3 for subjects between 18 to 74 years of age

          3. Participant must have a projected life expectancy of at least 12 weeks.

          4. Participant must have adequate renal function as demonstrated by a creatinine
             clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by
             24-hour urine collection.

          5. Participant must have adequate liver function as demonstrated by:

               -  aspartate aminotransferase (AST) ≤ 3.0 × ULN*

               -  alanine aminotransferase (ALT) ≤ 3.0 × ULN*

               -  bilirubin ≤ 1.5 × ULN*

                    -  Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN

             (*Unless considered to be due to leukemic organ involvement.)

          6. Female participants must be either postmenopausal defined as:

               -  Age > 55 years with no menses for 12 or more months without an alternative
                  medical cause.

               -  Age ≤ 55 years with no menses for 12 or more months without an alternative
                  medical cause AND a follicle-stimulating hormone (FSH) level > 40 IU/L.

             OR

               -  Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

             OR

               -  A woman of childbearing potential (WOCBP) practicing at least one protocol
                  specified method of birth control starting at Study Day 1 through at least 180
                  days after the last dose of study drug.

          7. Male participants who are sexually active, must agree, from Study Day 1 through at
             least 180 days after the last dose of study drug, to practice protocol specified
             methods of contraception. Male subjects must agree to refrain from sperm donation from
             initial study drug administration through at least 180 days after the last dose of
             study drug.

          8. Females of childbearing potential must have negative results for pregnancy test
             performed:

               -  At Screening with a serum sample obtained within 14 days prior to the first study
                  drug administration, and

               -  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.

               -  Subjects with borderline pregnancy tests at Screening must have a serum pregnancy
                  test ≥ 3 days later to document continued lack of a positive result.

          9. Participant must voluntarily sign and date an informed consent form, approved by an
             Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
             initiation of any screening or study-specific procedures.

        Exclusion Criteria:

          1. Participant has received any prior treatment for AML with the exception of
             hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment
             for myelodysplastic syndrome is allowed except for use of cytarabine.

          2. Participant had an antecedent myeloproliferative neoplasm (MPN) including
             myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous
             leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1
             translocation.

          3. Participants that have acute promyelocytic leukemia (APL).

          4. Participant has known central nervous system (CNS) involvement with AML.

          5. Participant has known human immunodeficiency virus (HIV) infection (due to potential
             drug-drug interactions between antiretroviral medications and venetoclax). HIV testing
             will be performed at Screening, if required per local guidelines or institutional
             standards.

          6. Participant is known to be positive for hepatitis B virus (HBV), or hepatitis C virus
             (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on
             antivirals (non-exclusionary medications) are not excluded.

          7. Participant has received strong or moderate cytochrome P450 3A4 (CYP3A) inducers 7
             days prior to the initiation of study treatment.

               -  Chinese subjects are excluded from receiving strong and/or moderate CYP3A
                  inhibitors 7 days prior to the initiation of study treatment through the end of
                  intensive pharmacokinetic (PK) collection (24 hours post dose on Cycle 1 Day 10).

          8. Participant has consumed grapefruit, grapefruit products, Seville oranges (including
             marmalade containing Seville oranges) or star fruit within 3 days prior to the
             initiation of study treatment.

          9. Participant has cardiovascular disability status of New York Heart Association Class >
             2. Class 2 is defined as cardiac disease which subjects are comfortable at rest but
             ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain.
             Class 3 is defined as cardiac disease which subjects are comfortable at rest but less
             than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as
             cardiac disease which subjects have an inability to carry on any physical activity
             without discomfort, symptoms of heart failure at rest, and if any physical activity is
             undertaken then discomfort increases.

         10. 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 LDAC that in
             the opinion of the investigator would adversely affect his/her participating in this
             study.

         11. Participant has a malabsorption syndrome or other condition that precludes enteral
             route of administration.

         12. Participant exhibits evidence of other clinically significant uncontrolled systemic
             infection requiring therapy (viral, bacterial or fungal).

         13. Participant 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.

         14. Participant has a white blood cell count > 25 × 10^9/L. (Note: hydroxyurea
             administration or leukapheresis is permitted to meet this criterion).

         15. Previous treatment with venetoclax and/or current participation in any other research
             study with investigational products.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:From randomization until the primary analysis cut-off date of February 15 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
Safety Issue:
Description:Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology.

Secondary Outcome Measures

Measure:Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML: CR: No morphologic evidence of AML and absolute neutrophil count (ANC) ≥ 10³/μL (1,000/μL), platelets ≥ 10⁵/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, the CRi criteria are met. Participants who had no IWG disease assessments were considered to be non-responders.
Measure:Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh)
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) at any time point during the study assessed by the investigator. CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is a derived response based on bone marrow blast and hematology lab values, achieved when the following criteria are met: Bone marrow with < 5% blasts and Peripheral blood neutrophil count of > 0.5 × 10³/μL and Peripheral blood platelet count of > 0.5 × 10⁵/μL and A 1 week platelet transfusion-free period prior to the hematology lab collection. Participants with no disease assessments were considered to be non-responders.
Measure:Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Initiation of Cycle 2
Time Frame:Cycle 1, 28 days
Safety Issue:
Description:The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) before initiation of Cycle 2, assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML: CR: No morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red cell transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except for RBC transfusion independence, CRi criteria are met. Participants who had no IWG disease assessments were considered to be non-responders.
Measure:Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR + CRh) by Initiation of Cycle 2
Time Frame:Cycle 1, 28 days
Safety Issue:
Description:The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) before initiation of Cycle 2 assessed by the investigator. CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is a derived response based on bone marrow blast and hematology lab values, achieved when when the following criteria are met: Bone marrow with < 5% blasts and Peripheral blood neutrophil count of > 0.5 × 10³/μL and Peripheral blood platelet count of > 0.5 × 10⁵/μL and A 1-week platelet transfusion-free period prior to the hematology lab collection. Participants with no disease assessments were considered to be non-responders.
Measure:Percentage of Participants With Complete Remission
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The complete remission rate is defined as the percentage of participants with complete remission (CR) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML. CR is defined as no morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. Participants who had no IWG disease assessments were considered to be non-responders.
Measure:Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a
Time Frame:Baseline and Day 1 of Cycles 3, 5, 7, and 9
Safety Issue:
Description:PROMIS Fatigue SF 7a is a seven-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always. The PROMIS Fatigue 7a score is calculated as a T-score, which is a standardized score with a mean of 50 (based on the average for the United States general population) and a standard deviation (SD) of 10. Higher scores indicate higher levels of fatigue. A decrease in score (negative change from Baseline) indicates improvement in fatigue; the minimum important difference used in this study was 3 points.
Measure:Change From Baseline in Global Health Status / Quality of Life
Time Frame:Baseline and Day 1 of Cycles 3, 5, 7, and 9
Safety Issue:
Description:The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) consists of a Global Health Status/Quality of Life (GHS/QoL) scale, a Financial Difficulties scale, 5 functional scales (Cognitive, Social, Physical, Emotional, and Role Functioning), and 8 symptom scales/items (Fatigue, Insomnia, Appetite Loss, Pain, Constipation, Diarrhea, Dyspnea, and Nausea and Vomiting). The GHS/QoL scale includes 2 questions in which participants were asked to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The 2 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life.
Measure:Event-free Survival (EFS)
Time Frame:From randomization until the primary analysis cut-off date of February 15, 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
Safety Issue:
Description:Event-free survival is defined as the time from randomization to the date of progressive disease (PD), confirmed morphologic relapse from CR or CRi, treatment failure (failure to achieve CR, CRi or morphologic leukemia free state (MLFS) after at least 6 cycles of study treatment), or death from any cause, assessed by the investigator according to the modified IWG criteria. PD: > 50% increase in marrow blasts (minimum 15% increase required if blasts < 30% at baseline); or persistent marrow blast > 70% for ≥ 3 months; without at least a 100% improvement in ANC to an absolute level > 0.5 × 10⁹/L, and/or platelets to > 50 × 10⁹/L non-transfused; or 50% increase in peripheral blasts to > 25 × 10⁹/L; or New extramedullary disease Participants with no events prior to the cut-off date were censored at their last assessment date; participants with no events prior to post-treatment therapy initiated before the cut-off date were censored on the start date of post-treatment therapy.
Measure:Percentage of Participants With Post Baseline Red Blood Cell (RBC) Transfusion Independence
Time Frame:From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
Safety Issue:
Description:The post baseline red blood cell (RBC) transfusion independence rate was calculated as the percentage of participants who achieved RBC transfusion independence post baseline. RBC transfusion independence is defined as a period of at least 56 consecutive days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.
Measure:Percentage of Participants With Post Baseline Platelet Transfusion Independence
Time Frame:From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
Safety Issue:
Description:The post baseline platelet transfusion independence rate was calculated as the percentage of participants who achieved platelet transfusion independence post Baseline. Platelet transfusion independence is defined as a period of at least 56 consecutive days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut--off date, whichever occurred earlier.
Measure:Percentage of Participants With RBC Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
Time Frame:From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
Safety Issue:
Description:The rate of conversion was calculated as the percentage of participants who were post-baseline RBC transfusion independent among participants who had an RBC transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). RBC transfusion independence is defined as a period of at least 56 days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.
Measure:Percentage of Participants With Platelet Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
Time Frame:From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
Safety Issue:
Description:The rate of conversion was calculated as the percentage of participants who were post-baseline platelet transfusion independent among participants who had a platelet transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). Platelet transfusion independence is defined as a period of at least 56 days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.
Measure:Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) and Minimal Residual Disease (MRD) Response
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The percentage of participants with complete remission or complete remission with incomplete blood count recovery AND minimal residual disease (MRD) as assessed by the investigator. Response was based on the modified IWG response criteria for AML: CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria are met. MRD response (at lowest-point MRD value) was defined as having less than 10-³ residual blasts per leukocyte measured in the bone marrow, per European LeukemiaNet (ELN) recommendations. Participants who had no disease or MRD assessments were considered to be non-responders.
Measure:Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) and Minimal Residual Disease (MRD) Response
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The percentage of participants with complete remission or complete remission with partial hematologic recovery (CRh) AND MRD response as assessed by the investigator. CR is defined according to the modified IWG response criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is achieved when the following criteria are met: Bone marrow with < 5% blasts and Peripheral blood neutrophil count of > 0.5 × 10³/μL and Peripheral blood platelet count of > 0.5 × 10⁵/μL and A 1 week platelet transfusion-free period prior to the hematology lab collection. MRD response (at lowest-point MRD value) was defined as less than 10-³ residual blasts per leukocyte measured in the bone marrow, per ELN recommendations. Participants who had no disease or MRD assessments were considered to be non-responders.
Measure:Overall Survival (OS) by Mutation Subgroups
Time Frame:From randomization until the primary analysis cut-off date of February 15, 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
Safety Issue:
Description:Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology. Overall survival was analyzed in participants with the following molecular markers: Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation FMS (Feline McDonough Sarcoma)-like tyrosine kinase 3 (FLT3) mutation
Measure:Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Mutation Subgroup
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML: CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria is met. Participants who had no IWG disease assessments were considered to be non-responders. Response was analyzed in participants with the following mutations: Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation FMS-like tyrosine kinase 3 (FLT3) mutation
Measure:Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) by Mutation Subgroup
Time Frame:Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
Safety Issue:
Description:The percentage of participants who achieved a complete remission or complete remission with partial hematologic recovery assessed by the investigator for participants with the following mutations: Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation FMS-like tyrosine kinase 3 (FLT3) mutation CR is defined according to the modified IWG criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is achieved when the following criteria are met: Bone marrow with < 5% blasts and Peripheral blood neutrophil count > 0.5 × 10³/μL and Peripheral blood platelet count > 0.5 × 10⁵/μL and A 1 week platelet transfusion-free period prior to hematology lab collection. Participants with no disease assessments were considered non-responders

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Acute Myeloid Leukemia
  • Leukemia
  • Treatment naïve
  • Venetoclax
  • Cytarabine

Last Updated

January 6, 2021