Trial Outcomes & Findings for Metabolically Optimized, Non-cytotoxic Low Dose Weekly Decitabine/Venetoclax in MDS and AML (NCT NCT05184842)

NCT ID: NCT05184842

Last Updated: 2026-01-05

Results Overview

The percentage of participants who are able to continue on treatment without dose interruptions or delays was defined as not having to delay or interrupt treatment due to toxicity or intolerability for more than two weeks during the 12-week induction period.

Recruitment status

RECRUITING

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

Up to 12 weeks

Results posted on

2026-01-05

Participant Flow

Between April 2022 and September 2023, 31 patients were enrolled. Nearly half of the patients were from diverse racial and ethnic backgrounds reflecting the demographics of an inner-city hospital in the Bronx, New York City.

31 patients were consented/enrolled and comprised the Primary Outcome Measure analysis. Enrollment in progress at the time of this submission. The Primary Outcome Measure has been met and Results are being reported for the 31 participants who comprised the Primary Outcome Measure.

Participant milestones

Participant milestones
Measure
Decitabine/Venetoclax (Single Arm)
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg subcutaneous (SQ) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Study
STARTED
31
Overall Study
COMPLETED
31
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

21 of the 31 patients were part of the AML cohort.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Decitabine/Venetoclax (Single Arm)
n=31 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Age, Continuous
67.5 years
n=4 Participants • 4 of the 31 patients were part of the 'Other' (non AML or non HR-MDS) cohort.
Age, Customized
> 75 years old
0 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Age, Customized
< 75 years old
4 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Sex: Female, Male
Female
2 Participants
n=4 Participants • 4 patients were part of the 'Other' cohort. This cohort was inclusive of patients with MDS/myeloproliferative neoplasm, chronic myelomonocytic leukemia, and myelofibrosis.
Sex: Female, Male
Male
2 Participants
n=4 Participants • 4 patients were part of the 'Other' cohort. This cohort was inclusive of patients with MDS/myeloproliferative neoplasm, chronic myelomonocytic leukemia, and myelofibrosis.
Race/Ethnicity, Customized
White
0 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Race/Ethnicity, Customized
Black
1 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Race/Ethnicity, Customized
Hispanic
2 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Race/Ethnicity, Customized
Asian
1 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Region of Enrollment
United States
31 Participants
n=31 Participants
Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale
ECOG PS = 0
13 Participants
n=31 Participants
Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale
ECOG PS = 1
14 Participants
n=31 Participants
Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale
ECOG PS = 2
4 Participants
n=31 Participants
Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale
ECOG PS = 3
0 Participants
n=31 Participants
ECOG PS Scale - AML Cohort
ECOG PS = 0
7 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
ECOG PS Scale - AML Cohort
ECOG PS = 1
10 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
ECOG PS Scale - AML Cohort
ECOG PS = 2
4 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
ECOG PS Scale - AML Cohort
ECOG PS = 3
0 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
ECOG PS Scale - HR-MDS Cohort
ECOG PS = 0
4 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
ECOG PS Scale - HR-MDS Cohort
ECOG PS = 1
2 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
ECOG PS Scale - HR-MDS Cohort
ECOG PS = 2
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
ECOG PS Scale - HR-MDS Cohort
ECOG PS = 3
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
ECOG PS Scale - Other Cohort
ECOG PS = 0
2 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
ECOG PS Scale - Other Cohort
ECOG PS = 1
2 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Somatic mutations - AML Cohort
TP53
5 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
ECOG PS Scale - Other Cohort
ECOG PS = 2
0 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
ECOG PS Scale - Other Cohort
ECOG PS = 3
0 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Somatic mutations
IDH1 or IDH2
6 Participants
n=31 Participants
Somatic mutations
NPM1
1 Participants
n=31 Participants
Somatic mutations
FLT3 ITD
2 Participants
n=31 Participants
Somatic mutations
N/KRAS
4 Participants
n=31 Participants
Somatic mutations
TP53
11 Participants
n=31 Participants
Somatic mutations - AML Cohort
IDH1 or IDH2
6 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Somatic mutations - AML Cohort
NPM1
1 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Somatic mutations - AML Cohort
FLT3 ITD
2 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Somatic mutations - AML Cohort
N/KRAS
4 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Somatic Mutations - HR-MDS Cohort
IDH1 or IDH2
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Somatic Mutations - HR-MDS Cohort
NPM1
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Somatic Mutations - HR-MDS Cohort
FLT3 ITD
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Somatic Mutations - HR-MDS Cohort
N/KRAS
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Somatic Mutations - HR-MDS Cohort
TP53
6 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Baseline Transfusion Dependence
18 Participants
n=31 Participants
Baseline Transfusion Dependence - AML Cohort
11 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Baseline Transfusion Dependence - HR-MDS Cohort
5 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Baseline Transfusion Dependence - Other Cohort
2 Participants
n=4 Participants • 4 of the 31 patients were part of the 'Other' cohort.
Acute Myeloid Leukemia (AML) Type
de novo
15 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Acute Myeloid Leukemia (AML) Type
Secondary (or t-AML)
6 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Bone Marrow Blast Count
<30%
13 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Bone Marrow Blast Count
≥30%
8 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
European Leukemia Net (ELN) Risk Stratification Criteria
Adverse Risk
14 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
European Leukemia Net (ELN) Risk Stratification Criteria
Intermediate Risk
6 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
European Leukemia Net (ELN) Risk Stratification Criteria
Favorable Risk
1 Participants
n=21 Participants • 21 of the 31 patients were part of the AML cohort.
Revised International Prognostic Scoring System (IPSS-R) Risk Category
Very low-risk: ≤1.5
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Revised International Prognostic Scoring System (IPSS-R) Risk Category
Low-risk: 1.5 - 3
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Revised International Prognostic Scoring System (IPSS-R) Risk Category
Intermediate-risk: 3 - 4.5
0 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Revised International Prognostic Scoring System (IPSS-R) Risk Category
High-risk: 4.5 - 6
1 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.
Revised International Prognostic Scoring System (IPSS-R) Risk Category
Very high-risk: >6
5 Participants
n=6 Participants • 6 of the 31 patients were part of the HR-MDS cohort.

PRIMARY outcome

Timeframe: Up to 12 weeks

The percentage of participants who are able to continue on treatment without dose interruptions or delays was defined as not having to delay or interrupt treatment due to toxicity or intolerability for more than two weeks during the 12-week induction period.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=31 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays
Patients able to continue treatment during induction period without dose interruptions or delays
28 Participants
Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays
Patients who missed one or more doses during induction period
3 Participants
Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays
Patients requiring dose reduction(s) during induction period
0 Participants

SECONDARY outcome

Timeframe: Up to 3 months

Percentage of participants with CR + CRi will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count (ANC) \> 1000/microliter (mcL), platelets \> 100,000/mcL, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤ 1000/mcL or platelets ≤ 100,000/mcL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months

A response of CRh is defined as Bone marrow with \<5% blasts, peripheral blood neutrophil count \>0.5\*10\^3/mcL and peripheral blood platelet count \>0.5\*10\^5/mcL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Rate of hospitalization will be defined as any hospitalization for complication related to myeloid malignancy or treatment. Initial admission for diagnosis or initiation of therapy will not be considered an event. For purposes of this study the rate of hospitalization will be defined as a percentage of participants who meet these criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Infection rate requiring hospitalization will be defined as being hospitalized due to a diagnosed infection or sepsis. For purposes of this study infection rate will be summarized as the percentage of patients who are diagnosed to have an infection or sepsis.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort.

Median OS is reported in patients with AML at the time of censoring of data for the Primary Outcome analysis. For purposes of this study, OS refers to the duration of time from treatment initiation until a patient's death from any cause.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=21 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Survival (OS) in AML Patients
16.1 months
Interval 11.3 to
An upper limit for the 95% Confidence Interval was unable to be reached for OS due to ongoing survival in some AML patients at the time of cutoff for data analysis (i.e., \~21 months).

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 6 patients who comprised the Primary Outcome analysis were part of the HR-MDS cohort.

Median OS is reported in patients with HR-MDS at the time of censoring of data for the Primary Outcome analysis. For purposes of this study, OS refers to the duration of time from treatment initiation until a patient's death from any cause.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=6 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Survival in HR-MDS Patients
9.6 months
Interval 8.5 to
An upper limit for the 95% Confidence Interval was unable to be reached due for OS to ongoing survival in some HR-MDS patients at the time of cutoff for data analysis (i.e., \~21 months).

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort.

ORR in patients with AML was determined by ITT analysis. ORR was defined by summarizing and calculating the number/percentage of patients with CR + CRi + Morphologic Leukemia-free State (MLFS), based on European LeukemiaNet (ELN) criteria. CR is defined as absolute neutrophil count (ANC) \> 1000/microliter (mcL), platelets \> 100,000/mcL, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤ 1000/mcL or platelets ≤ 100,000/mcL. MLFS is defined as bone marrow blasts \<5%; absence of blasts with Auer rods; and absence of extramedullary disease; no hematologic recovery required. Patients who have any response will be permitted to continue treatment until relapse or progression of disease. Results are summarized using basic descriptive statistics.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=21 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Response Rate (ORR) in Patients With AML by Intention-to-treat (ITT) Analysis
12 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort.

Best Overall Response was determined in patients with AML who were analyzed by ITT analysis. The number/percentage of patients with Complete Remission (CR), Complete Remission with incomplete hematologic recovery (CRi), Morphologic Leukemia-free State (MLFS), and No Response is summarized based on ELN criteria summarized in corresponding Outcome Measures.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=21 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Best Overall Response in Patients With AML Based on ITT Analysis
CR
10 Participants
Best Overall Response in Patients With AML Based on ITT Analysis
CRi
1 Participants
Best Overall Response in Patients With AML Based on ITT Analysis
MLFS
1 Participants
Best Overall Response in Patients With AML Based on ITT Analysis
No Response
9 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort. Results for 2 of the 21 patients were not evaluable by ITT-PP analysis.

ORR in patients with AML was also determined by ITT-PP analysis. ORR was defined by summarizing and calculating the number/percentage of patients with CR + CRi + Morphologic Leukemia-free State (MLFS), based on European LeukemiaNet (ELN) criteria. CR is defined as absolute neutrophil count (ANC) \> 1000/microliter (mcL), platelets \> 100,000/mcL, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤ 1000/mcL or platelets ≤ 100,000/mcL. MLFS is defined as bone marrow blasts \<5%; absence of blasts with Auer rods; and absence of extramedullary disease; no hematologic recovery required. Patients who have any response will be permitted to continue treatment until relapse or progression of disease. Results are summarized using basic descriptive statistics.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=19 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Response Rate in Patients With AML by Intention-to-treat Per Protocol (ITT-PP) Analysis
12 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort. Results for 2 of the 21 patients were not evaluable by ITT-PP analysis.

Best Overall Response was also determined in patients with AML who were analyzed by ITT-PP analysis. The number/percentage of patients with Complete Remission (CR), Complete Remission with incomplete hematologic recovery (CRi), Morphologic Leukemia-free State (MLFS), and No Response is summarized based on ELN criteria summarized in corresponding Outcome Measures.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=19 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Best Overall Response in Patients With AML Based on ITT-PP Analysis
CR
10 Participants
Best Overall Response in Patients With AML Based on ITT-PP Analysis
CRi
1 Participants
Best Overall Response in Patients With AML Based on ITT-PP Analysis
MLFS
1 Participants
Best Overall Response in Patients With AML Based on ITT-PP Analysis
No Response
7 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 6 patients who comprised the Primary Outcome analysis were part of the HR-MDS cohort.

ORR was determined in patients with HR-MDS. ORR was defined by summarizing and calculating the number/percentage of patients with Complete Remission + marrow Complete Remission (CR + mCR) based on International Working Group (IWG) criteria. Based on IWG criteria CR and mCR are considered the best outcomes and used for this endpoint. CR is defined as Bone marrow (BM): ≤ 5% myeloblasts with normal maturation of all cell lines, dysplasia may persist. Peripheral Blood (PB): Hgb ≥ 11g/dL, Platelets ≥ 100 x 10\^9/L, Neutrophils ≥ 1.0 x 10\^9/L, Blasts 0%. mCR is defined as BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. PB: if Hematologic Improvement (HI) responses, should be noted in addition to mCR (in this study, mCR absent HI is NOT considered a response). All responses must last ≥ 4 weeks. Patients who have any response will be permitted to continue treatment until relapse or progression of disease. Results are summarized using basic descriptive statistics.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=6 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Overall Response Rate in Patients With HR-MDS
4 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 6 patients who comprised the Primary Outcome analysis were part of the HR-MDS cohort.

Best Overall Response was determined for patients with HR-MDS. The number/percentage of patients with Complete Remission (CR), marrow Complete Remission (mCR), and No Response is summarized based on IWG criteria. The summary also includes the number/percentage of patients who demonstrated Complete Remission with incomplete hematologic recovery (CRi).

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=6 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Best Overall Response in Patients With HR-MDS
CR
3 Participants
Best Overall Response in Patients With HR-MDS
mCR
1 Participants
Best Overall Response in Patients With HR-MDS
CRi
2 Participants
Best Overall Response in Patients With HR-MDS
No Response
0 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort.

Median DOR was determined for AML patients who comprised the Primary Outcome Measure analysis. DOR was evaluated from the time of response after 12 weeks of induction until disease progression.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=21 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Duration of Response (DOR) in AML Patients
5.5 months
Interval 3.9 to
An upper limit for the 95% Confidence Interval for DOR was unable to be reached due to some AML patients continuing to respond to treatment at the time of cutoff for data analysis (i.e., \~21 months).

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 6 patients who comprised the Primary Outcome analysis were part of the HR-MDS cohort.

Median DOR was determined for HR-MDS patients who comprised the Primary Outcome Measure analysis. DOR was evaluated from the time of response after 12 weeks of induction until disease progression.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=6 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Duration of Response (DOR) in HR-MDS Patients
5.2 months
Interval 4.8 to
An upper limit for the 95% Confidence Interval for DOR was unable to be reached due to some HR-MDS patients continuing to respond to treatment at the time of cutoff for data analysis (i.e., \~21 months).

POST_HOC outcome

Timeframe: 8 weeks

Mortality at 8 weeks was assessed for the 31 patients who were evaluated as part of the Primary Outcome Measure

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=31 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Mortality
0 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort.

The number/percentage of AML patients analyzed by ITT who achieved Measurable Residual Disease (MRD) negativity was determined by multiparameter flow cytometry (MFC). Achieving MRD negativity after achieving remission in a cancer treatment is associated is associated with longer remissions, potentially longer survival rates, and a lower risk of relapse.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=21 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT
9 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 21 patients who comprised the Primary Outcome analysis were part of the AML cohort. Results for 2 of the 21 patients were not evaluable by ITT-PP analysis.

The number/percentage of AML patients analyzed by ITT-PP who achieved Measurable Residual Disease (MRD) negativity was determined by multiparameter flow cytometry (MFC). Achieving MRD negativity after achieving remission in a cancer treatment is associated is associated with longer remissions, potentially longer survival rates, and a lower risk of relapse.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=19 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT-PP
9 Participants

POST_HOC outcome

Timeframe: At the time of censoring of data, up to ~21 months

Population: 6 patients who comprised the Primary Outcome analysis were part of the HR-MDS cohort.

The number/percentage of HR-MDS patients achieving Measurable Residual Disease (MRD) negativity was determined by multiparameter flow cytometry (MFC). Achieving MRD negativity after achieving remission in a cancer treatment is associated is associated with longer remissions, potentially longer survival rates, and a lower risk of relapse.

Outcome measures

Outcome measures
Measure
Decitabine/Venetoclax (Single Arm)
n=6 Participants
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Measurable Residual Disease (MRD) in HR-MDS Patients
4 Participants

Adverse Events

Decitabine/Venetoclax (Single Arm)

Serious events: 0 serious events
Other events: 28 other events
Deaths: 4 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Decitabine/Venetoclax (Single Arm)
n=31 participants at risk
Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitabine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ). Venetoclax: Venetoclax 400 mg po on days 1, 8, 15 and 28 of each cycle (28day cycle) Decitabine: Decitabine 0.2 mg/kg SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)
Gastrointestinal disorders
Nausea
32.3%
10/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Vomiting
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Diarrhea
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Constipation
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
General disorders
Fatigue
41.9%
13/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Nervous system disorders
Dizziness
9.7%
3/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
General disorders
Weakness
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Dyspnea
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Renal and urinary disorders
Acute Kidney Injury
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Cough
22.6%
7/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Sore Throat
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Dysphagia
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Congestion
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
General disorders
Edema limbs
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Nervous system disorders
Peripheral Neuropathy
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Nervous system disorders
Headache
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
General disorders
Pain
9.7%
3/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Skin and subcutaneous tissue disorders
Hyperhidrosis
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Metabolism and nutrition disorders
Decreased Appetite
16.1%
5/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Investigations
Creatinine Increased
29.0%
9/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Investigations
Alanine aminotransferase (ALT) increased
41.9%
13/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Investigations
Aspartate aminotransferase (AST) increased
25.8%
8/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Investigations
Blood Bilirubin Increased
41.9%
13/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Blood and lymphatic system disorders
Febrile Neutropenia
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
General disorders
Fever
9.7%
3/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Blood and lymphatic system disorders
Bone Marrow Hypocellular
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Hypoxia
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Respiratory, thoracic and mediastinal disorders
Lung Infection
16.1%
5/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Bacteremia
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Skin Infection
9.7%
3/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Urinary Tract Infection
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
COVID-19
12.9%
4/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Respiratory Syncytial Virus (RSV)
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Norovirus
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Infections and infestations
Sinusitis
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Colitis
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Gastrointestinal disorders
Mucositis Oral
6.5%
2/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.
Hepatobiliary disorders
Cholecystitis
3.2%
1/31 • All adverse events that occur on or after day 1 of cycle 1 through 30 days after the final dose of study drug (end of treatment) will be reported, up to approximately 24 months total.

Additional Information

Mendel Goldfinger, MD

Montefiore Medical Center

Phone: 718-920-4826

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place