A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia
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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: NCT02287233 |
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Recruitment Status :
Completed
First Posted : November 10, 2014
Results First Posted : August 29, 2022
Last Update Posted : August 29, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myelogenous Leukemia AML | Drug: Venetoclax Drug: Cytarabine | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 94 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | December 31, 2014 |
| Actual Primary Completion Date : | August 10, 2021 |
| Actual Study Completion Date : | August 10, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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. |
Drug: Venetoclax
Venetoclax will be taken orally once daily.
Other Names:
Drug: Cytarabine Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle. |
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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. |
Drug: Venetoclax
Venetoclax will be taken orally once daily.
Other Names:
Drug: Cytarabine Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle. |
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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. |
Drug: Venetoclax
Venetoclax will be taken orally once daily.
Other Names:
Drug: Cytarabine Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle. |
- Phase 1: Number of Participants With Dose-limiting Toxicities [ Time Frame: Up to 28 days (Cycle 1) ]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.
- Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax [ Time Frame: 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) ]The highest concentration that a drug achieves in the blood after administration in a dosing interval.
- Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [ Time Frame: 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) ]The time at which the maximum plasma concentration (Cmax) is observed.
- Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax [ Time Frame: 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) ]
- Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine [ Time Frame: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose. ]The highest concentration that a drug achieves in the blood after administration in a dosing interval.
- Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine [ Time Frame: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose. ]The time at which the maximum plasma concentration (Cmax) is observed.
- Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine [ Time Frame: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose. ]
- Overall Response Rate [ Time Frame: 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. ]
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.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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. ]
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.
- Complete Remission Rate [ Time Frame: 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. ]
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.
- Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate [ Time Frame: 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. ]
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.
- CR Plus CRi Rate by Initiation of Cycle 2 [ Time Frame: Cycle 2, Day 1 ]
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.
- Time to First Response of CR + CRi [ Time Frame: 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. ]
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.
- Time to Best Response of CR + CRi [ Time Frame: 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. ]
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.
- Complete Remission With Partial Hematologic Recovery (CRh) Rate [ Time Frame: 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. ]
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.
- CR Plus CRh Rate [ Time Frame: 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. ]
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.
- CR Plus CRh Rate by Initiation of Cycle 2 [ Time Frame: Cycle 2, Day 1 ]
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.
- Time to First Response of CR Plus CRh [ Time Frame: 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. ]
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.
- Time to Best Response of CR Plus CRh [ Time Frame: 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. ]
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.
- Best Response Based on IWG Criteria [ Time Frame: 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. ]
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%.
- Duration of Complete Response [ Time Frame: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7) ]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.
- Duration of CR Plus CRi [ Time Frame: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7) ]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.
- Duration of CRi [ Time Frame: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7) ]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.
- Duration of CR Plus CRh [ Time Frame: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7) ]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.
- Overall Survival (OS) [ Time Frame: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7) ]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.
- Post Baseline Transfusion Independence Rate [ Time Frame: 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. ]
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.
- Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline [ Time Frame: 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. ]
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.
- Duration of Post Baseline Transfusion Independence [ Time Frame: 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. ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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.
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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.
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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
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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.
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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)
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).
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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.
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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).
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02287233
| United States, Kansas | |
| Univ Kansas Med Ctr /ID# 131175 | |
| Kansas City, Kansas, United States, 66160 | |
| United States, New York | |
| Weill Cornell Medical College /ID# 131170 | |
| New York, New York, United States, 10065 | |
| United States, Pennsylvania | |
| University of Pittsburgh MC /ID# 131168 | |
| Pittsburgh, Pennsylvania, United States, 15260 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center /ID# 131177 | |
| Nashville, Tennessee, United States, 37232-0011 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center /ID# 131178 | |
| Seattle, Washington, United States, 98109-1024 | |
| Australia, New South Wales | |
| Calvary Mater Newcastle /ID# 136076 | |
| Waratah, New South Wales, Australia, 2298 | |
| Australia, Victoria | |
| Alfred Health /ID# 131180 | |
| Melbourne, Victoria, Australia, 3004 | |
| Germany | |
| Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 133979 | |
| Hamburg, Germany, 20246 | |
| Italy | |
| Duplicate_A.O.U. Policlinico S.Orsola-Malpighi /ID# 131183 | |
| Bologna, Emilia-Romagna, Italy, 40138 | |
| Study Director: | ABBVIE INC. | AbbVie |
Documents provided by AbbVie:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT02287233 |
| Other Study ID Numbers: |
M14-387 2014-002610-23 ( EudraCT Number ) |
| First Posted: | November 10, 2014 Key Record Dates |
| Results First Posted: | August 29, 2022 |
| Last Update Posted: | August 29, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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, analyses plans, 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 Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/ |
| 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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ |
| URL: | https://vivli.org/ourmember/abbvie/ |
| 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 |
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Myelogenous Leukemia Treatment Naive AML Untreated AML |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms Cytarabine Venetoclax Antimetabolites, Antineoplastic |
Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |