search
Back to results

A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia

Primary Purpose

Acute Myelogenous Leukemia, AML

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Venetoclax
Cytarabine
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring Myelogenous Leukemia, Treatment Naive AML, Untreated AML

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

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.

Sites / Locations

  • Univ Kansas Med Ctr /ID# 131175
  • Weill Cornell Medical College /ID# 131170
  • University of Pittsburgh MC /ID# 131168
  • Vanderbilt University Medical Center /ID# 131177
  • Fred Hutchinson Cancer Research Center /ID# 131178
  • Calvary Mater Newcastle /ID# 136076
  • Alfred Health /ID# 131180
  • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 133979
  • Duplicate_A.O.U. Policlinico S.Orsola-Malpighi /ID# 131183

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1: 600 mg Venetoclax + LDAC

Phase 1: 800 mg Venetoclax + LDAC

Phase 2: 600 mg Venetoclax + LDAC

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants With Dose-limiting Toxicities
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
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
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
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine
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
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
Overall Response Rate
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)
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.

Secondary Outcome Measures

Complete Remission Rate
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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.

Full Information

First Posted
November 6, 2014
Last Updated
August 3, 2022
Sponsor
AbbVie
Collaborators
Genentech, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02287233
Brief Title
A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
December 31, 2014 (Actual)
Primary Completion Date
August 10, 2021 (Actual)
Study Completion Date
August 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Genentech, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia, AML
Keywords
Myelogenous Leukemia, Treatment Naive AML, Untreated AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: 600 mg Venetoclax + LDAC
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 800 mg Venetoclax + LDAC
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: 600 mg Venetoclax + LDAC
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
GDC-0199, ABT-199, VENCLEXTA®
Intervention Description
Venetoclax will be taken orally once daily.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants With Dose-limiting Toxicities
Description
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.
Time Frame
Up to 28 days (Cycle 1)
Title
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax
Description
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
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)
Title
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Description
The time at which the maximum plasma concentration (Cmax) is observed.
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)
Title
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)
Title
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine
Description
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
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.
Title
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine
Description
The time at which the maximum plasma concentration (Cmax) is observed.
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.
Title
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.
Title
Overall Response Rate
Description
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.
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.
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
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.
Secondary Outcome Measure Information:
Title
Complete Remission Rate
Description
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.
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.
Title
Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate
Description
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.
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.
Title
CR Plus CRi Rate by Initiation of Cycle 2
Description
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 Frame
Cycle 2, Day 1
Title
Time to First Response of CR + CRi
Description
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 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.
Title
Time to Best Response of CR + CRi
Description
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.
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.
Title
Complete Remission With Partial Hematologic Recovery (CRh) Rate
Description
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.
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.
Title
CR Plus CRh Rate
Description
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.
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.
Title
CR Plus CRh Rate by Initiation of Cycle 2
Description
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 Frame
Cycle 2, Day 1
Title
Time to First Response of CR Plus CRh
Description
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 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.
Title
Time to Best Response of CR Plus CRh
Description
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.
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.
Title
Best Response Based on IWG Criteria
Description
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%.
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.
Title
Duration of Complete Response
Description
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.
Time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
Title
Duration of CR Plus CRi
Description
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.
Time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
Title
Duration of CRi
Description
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.
Time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
Title
Duration of CR Plus CRh
Description
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.
Time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
Title
Overall Survival (OS)
Description
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.
Time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
Title
Post Baseline Transfusion Independence Rate
Description
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.
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.
Title
Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline
Description
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.
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.
Title
Duration of Post Baseline Transfusion Independence
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Univ Kansas Med Ctr /ID# 131175
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Weill Cornell Medical College /ID# 131170
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Pittsburgh MC /ID# 131168
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15260
Country
United States
Facility Name
Vanderbilt University Medical Center /ID# 131177
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-0011
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center /ID# 131178
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
Calvary Mater Newcastle /ID# 136076
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Alfred Health /ID# 131180
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 133979
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Duplicate_A.O.U. Policlinico S.Orsola-Malpighi /ID# 131183
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
IPD Sharing 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/
IPD Sharing URL
https://vivli.org/ourmember/abbvie/
Citations:
PubMed Identifier
30892988
Citation
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.
Results Reference
background
PubMed Identifier
35829925
Citation
Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.
Results Reference
derived
Links:
URL
https://www.rxabbvie.com/
Description
This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Learn more about this trial

A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia

We'll reach out to this number within 24 hrs