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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02287233
Registration number
NCT02287233
Ethics application status
Date submitted
6/11/2014
Date registered
10/11/2014
Date last updated
29/08/2022
Titles & IDs
Public title
A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia
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Scientific title
A Phase 1/2 Study of Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Subjects With Acute Myelogenous Leukemia Who Are = 60 Years of Age and Who Are Not Eligible for Standard Anthracycline-Based Induction Therapy
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Secondary ID [1]
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2014-002610-23
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Secondary ID [2]
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M14-387
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myelogenous Leukemia
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AML
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Cytarabine
Experimental: Phase 1: 600 mg Venetoclax + LDAC - Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.
Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Experimental: Phase 1: 800 mg Venetoclax + LDAC - Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.
Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Experimental: Phase 2: 600 mg Venetoclax + LDAC - Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.
Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Treatment: Drugs: Venetoclax
Venetoclax will be taken orally once daily.
Treatment: Drugs: Cytarabine
Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Phase 1: Number of Participants With Dose-limiting Toxicities
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Assessment method [1]
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Dose-limiting toxicities (DLTs) were determined during cycle 1 of the dose-escalation phase and defined as Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 grade 4 (life threatening requiring urgent intervention) or 5 (resulted in death) toxicity, excluding adverse events commonly caused by AML (eg, neutropenia, fever). Hematologic DLT was defined as failure of platelet recovery to 25 × 10^9/L or greater and absolute neutrophil count (ANC) to 0.5 × 10^9/L or greater within 14 days of the last dose of venetoclax in the absence of residual AML.
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Timepoint [1]
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Up to 28 days (Cycle 1)
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Primary outcome [2]
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Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax
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Assessment method [2]
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The highest concentration that a drug achieves in the blood after administration in a dosing interval.
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Timepoint [2]
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Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
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Primary outcome [3]
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Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
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Assessment method [3]
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The time at which the maximum plasma concentration (Cmax) is observed.
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Timepoint [3]
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Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
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Primary outcome [4]
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Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax
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Assessment method [4]
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Timepoint [4]
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Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
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Primary outcome [5]
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Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine
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Assessment method [5]
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The highest concentration that a drug achieves in the blood after administration in a dosing interval.
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Timepoint [5]
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Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
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Primary outcome [6]
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Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine
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Assessment method [6]
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The time at which the maximum plasma concentration (Cmax) is observed.
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Timepoint [6]
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Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
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Primary outcome [7]
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Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine
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Assessment method [7]
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Timepoint [7]
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Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
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Primary outcome [8]
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Overall Response Rate
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Assessment method [8]
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Overall response rate (ORR) is defined as the percentage of participants who achieved a complete remission (CR), complete remission with incomplete marrow recovery (CRi), or partial remission (PR) per the International Working Group (IWG) for AML response criteria, per investigator assessment.
CR: absolute neutrophil count (ANC) = 10^3 /µL, platelet counts = 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.
PR: all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
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Timepoint [8]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Primary outcome [9]
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Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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Assessment method [9]
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An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator rated the severity of each AE according to the CTCAE Version 4.0 and the following:
Grade 1: The AE is transient and easily tolerated (mild).
Grade 2: The AE causes discomfort and interrupts usual activities (moderate).
Grade 3: The AE causes considerable interference with usual activities and may be incapacitating (moderate to severe).
Grade 4: The AE is life threatening requiring urgent intervention.
Grade 5: The AE resulted in death.
The investigator assessed each event as either having a reasonable possibility or no reasonable possibility of being related to the use of study drug.
Treatment-emergent events are defined as events that began or worsened in severity after the first dose of study drug.
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Timepoint [9]
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From first dose of study drug until 30 days after last dose of study drug; median (minimum, maximum) duration of treatment was 4.1 (0.2, 62.8) months overall.
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Secondary outcome [1]
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Complete Remission Rate
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Assessment method [1]
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Complete remission (CR) rate is defined as the percentage of participants who achieved a complete remission at any time point during the study per the modified IWG criteria for AML and investigator assessment.
CR: absolute neutrophil count (ANC) = 10^3 /µL, platelet counts = 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
Participants who never achieved CR or had no IWG disease assessment were considered to be non-responders in the calculation of CR rate.
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Timepoint [1]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [2]
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Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate
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Assessment method [2]
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The percentage of participants who achieved a CR or CRi at any time point during the study per the modified IWG criteria for AML and investigator assessment.
CR: absolute neutrophil count (ANC) = 10^3 /µL, platelet counts = 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL
Participants who never achieved CR or CRi or had no IWG disease assessment were considered to be non-responders in the calculation of CR + CRi rate.
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Timepoint [2]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [3]
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CR Plus CRi Rate by Initiation of Cycle 2
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Assessment method [3]
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The percentage of participants who achieved a CR or CRi by initiation of Cycle 2 of study treatment per the modified IWG criteria for AML and investigator assessment.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRi: Lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.
Participants who never achieved CR or CRi or had no IWG disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRi rate by initiation of Cycle 2.
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Timepoint [3]
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Cycle 2, Day 1
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Secondary outcome [4]
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Time to First Response of CR + CRi
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Assessment method [4]
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The time to the first response of CR + CRi is defined as the time from the first date of study drug to the first response of CR or CRi per the IWG AML response criteria assessed by the investigator.
CR: absolute neutrophil count (ANC) = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.
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Timepoint [4]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [5]
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Time to Best Response of CR + CRi
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Assessment method [5]
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The time to the best response of CR + CRi is defined as the time from the first date of study drug to the best response of CR or CRi per the IWG AML response criteria assessed by the investigator.
CR: absolute neutrophil count (ANC) = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.
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Timepoint [5]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [6]
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Complete Remission With Partial Hematologic Recovery (CRh) Rate
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Assessment method [6]
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Complete remission with partial hematologic recovery is a derived response based on bone marrow blast and hematology laboratory values. CRh rate is defined as the percentage of participants who achieved CRh as the best response at any time point during the study.
A participant achieved a CRh when meeting the following criteria:
Bone marrow with < 5% blasts and
Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and
Peripheral blood platelet count of > 0.5 × 10^5 /µL and
A 1 week (= 7 days) platelet transfusion-free period prior to the hematology lab collection.
Participants who never achieved CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CRh rate.
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Timepoint [6]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [7]
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CR Plus CRh Rate
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Assessment method [7]
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CR + CRh rate is defined as the percentage of participants who achieved CR or CRh at any time point during the study.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:
Bone marrow with < 5% blasts and
Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and
Peripheral blood platelet count of > 0.5 × 10^5 /µL and
A 1 week (= 7 days) platelet transfusion-free period prior to the hematology lab collection.
Participants who never achieved CR/CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CR + CRh rate.
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Timepoint [7]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [8]
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CR Plus CRh Rate by Initiation of Cycle 2
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Assessment method [8]
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CR + CRh rate by initiation of Cycle 2 is defined as the percentage of participants who achieved CR or CRh by initiation of Cycle 2 of study treatment.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:
Bone marrow with < 5% blasts and
Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and
Peripheral blood platelet count of > 0.5 × 10^5 /µL and
A 1 week (= 7 days) platelet transfusion-free period prior to the hematology lab collection.
Participants who never achieved CR/CRh or did not have disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRh rate by initiation of Cycle 2.
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Timepoint [8]
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Cycle 2, Day 1
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Secondary outcome [9]
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Time to First Response of CR Plus CRh
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Assessment method [9]
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The time to the first response of CR + CRh is defined as the time from the first date of study drug to the first response of CR or CRh.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:
Bone marrow with < 5% blasts and
Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and
Peripheral blood platelet count of > 0.5 × 10^5 /µL and
A 1 week (= 7 days) platelet transfusion-free period prior to the hematology lab collection.
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Timepoint [9]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [10]
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Time to Best Response of CR Plus CRh
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Assessment method [10]
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The time to the best response of CR + CRh is defined as the time from the first date of study drug to the best response of CR or CRh.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.
CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:
Bone marrow with < 5% blasts and
Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and
Peripheral blood platelet count of > 0.5 × 10^5 /µL and
A 1 week (= 7 days) platelet transfusion-free period prior to the hematology lab collection.
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Timepoint [10]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [11]
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Best Response Based on IWG Criteria
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Assessment method [11]
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Best response determined using the IWG-AML response criteria during the course of treatment.
CR: ANC = 10^3 /µL, platelet counts = 10^5 /µL, RBC transfusion independence, and bone marrow with < 5% blasts;
CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL;
PR: all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate;
MLFS: < 5% blasts in an aspirate and/or bone marrow core sample;
RD: failure to achieve CR, CRi, PR; only including subjects surviving at least 7 days following completion of initial treatment cycle with evidence of persistent leukemia by blood and/or bone marrow examination;
PD: one or more of the following: = 50% decrement from maximum response levels in neutrophils or platelets; a reduction in hemoglobin by at least 2 g/dL; or transfusion dependence not due to other toxicities and bone marrow blast = 5%.
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Timepoint [11]
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Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
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Secondary outcome [12]
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Duration of Complete Response
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Assessment method [12]
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Duration of CR is defined as the time from date that a participant achieved CR to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the duration of CR analysis.
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Timepoint [12]
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Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
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Secondary outcome [13]
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Duration of CR Plus CRi
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Assessment method [13]
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Duration of CR + CRi is defined as the time from the date that a participant achieved CR or CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.
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Timepoint [13]
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Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
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Secondary outcome [14]
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Duration of CRi
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Assessment method [14]
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Duration of CRi is defined as the time from date that a participant achieved CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.
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Timepoint [14]
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Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
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Secondary outcome [15]
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Duration of CR Plus CRh
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Assessment method [15]
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Duration of CR + CRh is defined as the time from date that a participant achieved CR or CRh to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRh was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.
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Timepoint [15]
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Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
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Secondary outcome [16]
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Overall Survival (OS)
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Assessment method [16]
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Overall survival is defined as the time from the date of first dose to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study drug, or after the participant discontinued study drug. OS was estimated using Kaplan-Meier methodology. Participants who were still alive were censored at the analysis date.
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Timepoint [16]
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Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
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Secondary outcome [17]
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Post Baseline Transfusion Independence Rate
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Assessment method [17]
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Post baseline transfusion independence rate was estimated as the percentage of participants who achieved transfusion independence during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days (= 56 days) with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.
Results are reported for participants who achieved both RBC and platelet transfusion independence and for participants who received RBC transfusion independence and platelet transfusion independence.
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Timepoint [17]
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From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
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Secondary outcome [18]
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Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline
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Assessment method [18]
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Post baseline transfusion independence rate was estimated as the percentage of participants who achieved transfusion independence during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days (= 56 days) with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.
Results are reported for participants who achieved both RBC and platelet transfusion independence and for participants who received RBC transfusion independence and platelet transfusion independence.
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Timepoint [18]
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From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
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Secondary outcome [19]
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Duration of Post Baseline Transfusion Independence
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Assessment method [19]
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The duration of transfusion independence is defined as the first time period that a participant received no RBC/platelet transfusions for at least 56 days during the evaluation period.
Post-baseline transfusion independence is defined as a period of at least 56 days with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.
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Timepoint [19]
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From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
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Eligibility
Key inclusion criteria
- Participant must be greater than or equal to 65 years of age in Phase 1 and 2.
Participants enrolled in Cohort C must be either:
- greater than or equal to 75 years of age; OR
- greater than or equal to 60 to 74 years will be eligible if the participants has
at least one of the following co-morbidities, which make the participant unfit
for intensive chemotherapy:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 - 3;
- Cardiac history of congestive heart failure (CHF) requiring treatment or
ejection fraction less than or equal to 50% or chronic stable angina;
- Diffusion capacity of carbon monoxide (DLCO) less than or equal to 65% or
forced expiratory volume in one second (FEV1) less than or equal to 65%;
- Creatinine clearance greater than or equal to 30 mL/min to less than 45
ml/min (calculated by Cockcroft-Gault formula)
- Moderate hepatic impairment with total bilirubin greater than 1.5 to less
than or equal to 3.0 × upper limit of normal (ULN)
- Any other comorbidity that the physician judges to be incompatible with
intensive chemotherapy must be reviewed and approved by the study medical
monitor before study enrollment
- Participant must have a projected life expectancy of at least 12 weeks.
- Participant must have histological confirmation of AML and be ineligible for treatment
with a standard cytarabine and anthracycline induction regimen due to co-morbidity or
other factors.
- Participant must have received no prior treatment for AML with the exception of
hydroxyurea, allowed through the first cycle of study treatment. Note: Participant may
have been treated for prior Myelodysplastic Syndrome.
- Participant must have an ECOG performance status:
- of 0 to 2 for participants greater than equal to 75 years of age
- of 0 to 3 for participants greater than equal to 60 to 74 years of age, if 0 - 1
another co-morbidity is required to make participant eligible.
- Participant must have adequate renal function as demonstrated by a creatinine
clearance greater than or equal to 30 mL/min; determined via urine collection for
24-hour creatinine clearance or by the Cockcroft Gault formula.
- Participant must have adequate liver function as demonstrated by:
- aspartate aminotransferase (AST) less than or equal to 2.5 × ULN
- alanine aminotransferase (ALT) less than or equal to 2.5 × ULN
- bilirubin less than or equal to 1.5 × ULN for all participants age 75 and older
- Participants who are less than 75 years of age must have a bilirubin of less
than 3.0 × ULN.
Note: Participants with Gilbert's Syndrome may have a bilirubin greater than 1.5 × ULN per
discussion between the investigator and AbbVie medical monitor.
- Male participants must agree to refrain from unprotected sex and sperm donation from
initial study drug administration until 180 days after the last dose of study drug.
- 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.
- If female, participant must be either:
- Postmenopausal defined as no menses for 12 or more months without an alternative
medical cause OR
- Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy)
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Minimum age
60
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Participant has received treatment with cytarabine for a pre-existing myeloid
disorder.
- Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).
- Participant has known active central nervous system (CNS) involvement with AML.
- Participant has tested positive for human immunodeficiency virus (HIV).
- Participant has received the following within 7 days prior to the initiation of study
treatment:
- Strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin,
and St. John's wort.
- 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
greater than 2.
- Participant has a significant history of renal, neurologic, psychiatric,
endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other
medical condition that in the opinion of the investigator would adversely affect
his/her participating in this study.
- Participant has chronic respiratory disease that requires continuous oxygen use.
- Participant has a malabsorption syndrome or other condition that precludes enteral
route of administration.
- Participant exhibits evidence of other clinically significant uncontrolled
condition(s) including, but not limited to:
- Uncontrolled systemic infection requiring intravenous (IV) therapy (viral,
bacterial or fungal).
- Participant has a history of other malignancies prior to study entry, with the
exception of:
- Adequately treated in situ carcinoma of the breast or cervix uteri;
- 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.
- Participant has a white blood cell count greater than 25 × 10^9/L. Note: Hydroxyurea
is permitted to meet this criterion.
- Participant is a candidate for a bone marrow or stem cell transplant within 12 weeks
after study enrollment.
- Participant has a history of myeloproliferative neoplasm (MPN) including polycythemia
vera, myelofibrosis, essential thrombocythemia, or chronic myelogenous leukemia.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
31/12/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
10/08/2021
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Sample size
Target
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Accrual to date
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Final
94
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
0
0
Calvary Mater Newcastle /ID# 136076 - Waratah
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Recruitment hospital [2]
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0
Alfred Health /ID# 131180 - Melbourne
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Recruitment postcode(s) [1]
0
0
2298 - Waratah
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Recruitment postcode(s) [2]
0
0
3004 - Melbourne
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Kansas
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Country [2]
0
0
United States of America
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State/province [2]
0
0
New York
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Pennsylvania
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Tennessee
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Washington
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Country [6]
0
0
Germany
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State/province [6]
0
0
Hamburg
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Country [7]
0
0
Italy
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State/province [7]
0
0
Emilia-Romagna
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
AbbVie
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Address
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Country
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Other collaborator category [1]
0
0
Commercial sector/Industry
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Name [1]
0
0
Genentech, Inc.
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Address [1]
0
0
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Country [1]
0
0
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Ethics approval
Ethics application status
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Summary
Brief summary
This study consists of two parts: A Phase 1 dose-escalation part that will evaluate the
safety and pharmacokinetic profile of venetoclax in combination with low-dose cytarabine
(LDAC), define the maximum tolerated dose (MTD), and generate data to support a recommended
Phase 2 dose (RPTD) in treatment-naïve participants with acute myelogenous leukemia (AML);
and a Phase 2 part that will evaluate if the RPTD has sufficient efficacy and acceptable
toxicity to warrant further development of the combination therapy.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02287233
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Trial related presentations / publications
Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 May 20;37(15):1277-1284. doi: 10.1200/JCO.18.01600. Epub 2019 Mar 20.
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Public notes
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Contacts
Principal investigator
Name
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0
ABBVIE INC.
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Address
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AbbVie
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02287233
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