NCT02287233 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2022-08-29

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Phase 1: Number of Participants With Dose-limiting Toxicities

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outcome · POSTED

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax

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outcome · POSTED

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax

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outcome · POSTED

Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax

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outcome · POSTED

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine

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outcome · POSTED

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine

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outcome · POSTED

Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Complete Remission Rate

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outcome · POSTED

Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate

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outcome · POSTED

CR Plus CRi Rate by Initiation of Cycle 2

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outcome · POSTED

Time to First Response of CR + CRi

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outcome · POSTED

Time to Best Response of CR + CRi

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outcome · POSTED

Complete Remission With Partial Hematologic Recovery (CRh) Rate

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outcome · POSTED

CR Plus CRh Rate

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outcome · POSTED

CR Plus CRh Rate by Initiation of Cycle 2

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outcome · POSTED

Time to First Response of CR Plus CRh

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outcome · POSTED

Time to Best Response of CR Plus CRh

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outcome · POSTED

Best Response Based on IWG Criteria

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outcome · POSTED

Duration of Complete Response

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outcome · POSTED

Duration of CR Plus CRi

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outcome · POSTED

Duration of CRi

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outcome · POSTED

Duration of CR Plus CRh

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Post Baseline Transfusion Independence Rate

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outcome · POSTED

Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline

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outcome · POSTED

Duration of Post Baseline Transfusion Independence

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 60 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: Venetoclax
Drug: Cytarabine
label
Phase 1: 600 mg Venetoclax + LDAC
type
EXPERIMENTAL
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.
intervention Names
Drug: Venetoclax
Drug: Cytarabine
label
Phase 1: 800 mg Venetoclax + LDAC
type
EXPERIMENTAL
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 Names
Drug: Venetoclax
Drug: Cytarabine
label
Phase 2: 600 mg Venetoclax + LDAC
type
EXPERIMENTAL

interventions

arm Group Labels
Phase 1: 600 mg Venetoclax + LDAC
Phase 1: 800 mg Venetoclax + LDAC
Phase 2: 600 mg Venetoclax + LDAC
description
Venetoclax will be taken orally once daily.
name
Venetoclax
other Names
GDC-0199
ABT-199
VENCLEXTA®
type
DRUG
arm Group Labels
Phase 1: 600 mg Venetoclax + LDAC
Phase 1: 800 mg Venetoclax + LDAC
Phase 2: 600 mg Venetoclax + LDAC
description
Low-dose cytarabine will be administered subcutaneously on Days 1 to 10 of each 28-day cycle.
name
Cytarabine
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 94
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Phase 1: Number of Participants With Dose-limiting Toxicities
time Frame
Up to 28 days (Cycle 1)
description
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
measure
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)
description
The time at which the maximum plasma concentration (Cmax) is observed.
measure
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)
measure
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)
description
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
measure
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.
description
The time at which the maximum plasma concentration (Cmax) is observed.
measure
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.
measure
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.
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.
measure
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.
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.
measure
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.

secondary Outcomes

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.
measure
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.
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.
measure
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.
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.
measure
CR Plus CRi Rate by Initiation of Cycle 2
time Frame
Cycle 2, Day 1
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.
measure
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.
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.
measure
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.
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.
measure
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.
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.
measure
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.
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.
measure
CR Plus CRh Rate by Initiation of Cycle 2
time Frame
Cycle 2, Day 1
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.
measure
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.
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.
measure
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.
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%.
measure
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.
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.
measure
Duration of Complete Response
time Frame
Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Full 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.

Source references

references

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.
pmid
30892988
type
BACKGROUND
citation
Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Champion R, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Yamauchi T, Wang J, Strickland SA, Savona MR, Lin TL, Enjeti A, Tiong IS, Lee S, Roboz GJ, Popovic R, Jiang Q, Liu Z, Sun Y, Mendes W, Chyla B, DiNardo CD. Risk stratification of low-dose cytarabine and venetoclax in patients with AML ineligible for intensive chemotherapy. Blood Adv. 2026 Feb 24;10(4):987-998. doi: 10.1182/bloodadvances.2025017083.
pmid
41269778
type
DERIVED
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.
pmid
35829925
type
DERIVED