Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
Myeloid malignancies which include AML (acute myeloid leukemia) and MDS (myelodysplatic syndrome) are cancers of the bone marrow which lead to bone marrow failure. The bone marrow is the place or factory in the body where components of blood such as red cells, platelets and white cells are made. In bone marrow failure, the ability of the bone marrow to make these cells is decreased. The decreased bone marrow function is the result from abnormalities that develop in the malignant cells which prevent the normal maturation process by which bone marrow cells develop into red blood cells, white blood cells and platelets. The malignant cells in the bone marrow are not good at maturing to make the components of the blood that you need, they occupy space in the bone marrow and prevent the function of remaining normal bone marrow cells. DNA is a chemical substance within cells that stores information needed for cell growth and cell behavior. One approach to treating the malignant cells is to give chemotherapy which damages DNA within these cells and causes their death. Unfortunately, such therapy has side-effects, since even normal cells can be affected by the treatment. Decitabine is FDA approved for treatment of MDS and AML. Venetoclax is approved for AML in combination with Azacitidine for patients with AML or are over age 75 or unfit for chemotherapy. In this study, Decitabine and venetoclax will be administered using a low dose weekly schedule in an attempt to improve efficacy by decreasing the side effects often seen when these drugs are given at standard dosing.
Detailed description
The combination of Azacitidine and venetoclax (Aza/Ven) is FDA approved for patients AML \> 75 and/or unfit for induction chemotherapy. However, majority of patients receiving standard dosing of Aza/Ven require dose interruptions, treatment delays and dose reductions. In addition, Aza/ven has limited activity in various subgroups of myeloid malignancies such as P53 mutant MDS/AML. In the initial safety and tolerability phase of the study, 33 patients will be enrolled on this study, accounting for need for replacement subjects to evaluate endpoints. In the second expansion phase of the study up to 91 patients (including patients from the 1st stage), will be enrolled to obtain additional safety, tolerability and preliminary efficacy of the low dose regimen in selected subsets of patients with myeloid malignancies. As treatment with Hypomethylating agents (HMAs) requires extended drug exposure for efficacy, patients who do not complete 12 weeks of therapy for reasons other than disease progression or those who do not complete therapy due to toxicity or those who screen fail and do not start therapy, will be replaced. Any patient who starts therapy will be evaluable for safety. In the absence of overt disease progression or dose limiting toxicity, patients would be anticipated to remain on treatment for at least 12 weeks. After 12 weeks, patient may continue therapy if felt to be experiencing clinical benefit. The severe cytopenias encountered with Aza/ven is particularly challenging for patients with poor hematopoietic bone marrow reserve such as MDS and myelofibrosis (MF). Also some elderly patients with comorbidities cannot tolerate the prolonged cytopenias caused by Aza/ven. This pilot clinical trial will evaluate the tolerability of a non-cytotoxic regimen for patients with myeloid malignancies who either cannot tolerate or are not known to benefit from standard Aza/Ven dosing. This will be a single arm, open label pilot study of weekly dosing of subcutaneous decitabine and venetoclax. Patients will be treated for a minimum of 12 weeks in the absence of clear evidence of progressive disease. Patients who have any response will be permitted to continue treatment until relapse or progression of disease. Decitabine is given at a dose of 0.1-0.2 mg/kg/day for 1-2 days per week. All patients will receive at least one dose Decitabine every week. If decided by treating physician that the patient needs a more rapid debulking of high disease burden, a second dose can be added. If Decitabine is given twice a week, should preferably be given on two consecutive days. Venetoclax is dosed at 400 mg by mouth one day a week a day prior to the first decitabine dose. If patients are taking another CYP3A4 inhibitor dose adjustments should be made as recommended by pharmacist for a goal dose of venetoclax of 400 mg. If patient receives two days of decitabine a week, they still only take venetoclax on the day prior to the first dose of decitabine.
Interventions
DRUGVenetoclax
Venetoclax 400 mg po on days 1, 8, 15 and 22 of each cycle (28-day cycle)
DRUGDecitabine
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)
Sponsors
The V Foundation for Cancer Research
Icahn School of Medicine at Mount Sinai
Servier
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have a diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with a histopathologic diagnosis confirmed by hematopathology review * Indication for therapy with potential sensitivity to hypomethylating agents (HMA) therapy, defined as prior published evidence of response to HMA * Patients must be 18 years of age or older * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3 * Patients must have adequate end organ function defined as. * Aspartate aminotransferase (AST) and Alanine transaminase (ALT) \< 4× the upper limit of normal (ULN) * Bilirubin ≤ 2× the ULN (upper limit of normal). If elevated bilirubin is due to impaired conjugation (e.g., Gilbert's disease or concomitant medication) or disease related hemolysis, then direct bilirubin ≤ 1.5× the ULN * As decitabine and venetoclax have little renal metabolism, and have proven safety even in dialysis patients, renal function with a creatinine clearance ≥30 mL/min or on dialysis is allowed * Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures.
Exclusion criteria
* Acute promyelocytic leukemia (APL) * Core binding factor AML who are candidates for chemotherapy * Prior Treatment with azacitidine, decitabine or venetoclax * No other disease directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry * Currently pregnant or breast-feeding. Females of childbearing potential (FOCBP) must have negative serum pregnancy test within 72 hours from treatment start. (NOTE: FOCBP is any biologic female, regardless of sexual or gender orientation, having undergone tubal ligation, or remaining celibate by choice, who has not undergone a documented hysterectomy or bilateral oophorectomy or has had a menses any time in the preceding 12 months (therefore not naturally post-menopausal for \> 12 months) * Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to: 1. Ongoing or active infection. As patients with myeloid malignancies are prone to infections, if patients are actively being treated with appropriate antibiotics or antifungal therapy with clinical evidence of infection control, then they will be considered eligible for study. 2. Uncontrolled concurrent malignancy 3. Congestive heart failure of xNew York Heart Association (NYHA) class III/IV. Patients with compensated heart failure are permitted 4. Unstable angina pectoris 5. New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted 6. Decompensated liver cirrhosis (Child-Pugh score ≥12 or a Model for Enst-Stage Liver Disease (MELD) score ≥21 7. Psychiatric illness/social situations that would limit compliance with study requirements 8. Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results * Women of Child-Bearing Potential (WOCBP) and males that are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately * Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of Decitabine/venetoclax * Patients with uncontrolled active HIV infection, as this will further increase the risk for opportunistic infections. However, patients with HIV with undetectable viral load by polymerase chain reaction (PCR), without opportunistic infection, and on a stable regimen of antiretroviral therapy would be eligible * Known allergy or hypersensitivity to any component of decitabine or venetoclax formulations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | 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. |
| Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh) | 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. |
| Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi) | 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. |
| Rate of Hospitalization | 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. |
| Infection Rate Requiring Hospitalization | 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. |
| Post Baseline Transfusion Independence Rate | 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. |
Countries
United States
Contacts
Primary ContactMendel Goldfinger, MD
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 SQ (subcutaneous) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24) | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Decitabine/Venetoclax (Single Arm) |
|---|---|
| Acute Myeloid Leukemia (AML) Type de novo | 15 Participants |
| Acute Myeloid Leukemia (AML) Type Secondary (or t-AML) | 6 Participants |
| Age, Continuous | 75 years |
| Age, Customized < 75 years old | 12 Participants |
| Age, Customized > 75 years old | 1 Participants |
| Baseline Transfusion Dependence | 18 Participants |
| Baseline Transfusion Dependence - AML Cohort | 11 Participants |
| Baseline Transfusion Dependence - HR-MDS Cohort | 5 Participants |
| Baseline Transfusion Dependence - Other Cohort | 2 Participants |
| Bone Marrow Blast Count <30% | 13 Participants |
| Bone Marrow Blast Count ≥30% | 8 Participants |
| Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale ECOG PS = 0 | 13 Participants |
| Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale ECOG PS = 1 | 14 Participants |
| Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale ECOG PS = 2 | 4 Participants |
| Eastern Clinical Oncology Group (ECOG) Performance Status (PS) Scale ECOG PS = 3 | 0 Participants |
| ECOG PS Scale - AML Cohort ECOG PS = 0 | 7 Participants |
| ECOG PS Scale - AML Cohort ECOG PS = 1 | 10 Participants |
| ECOG PS Scale - AML Cohort ECOG PS = 2 | 4 Participants |
| ECOG PS Scale - AML Cohort ECOG PS = 3 | 0 Participants |
| ECOG PS Scale - HR-MDS Cohort ECOG PS = 0 | 4 Participants |
| ECOG PS Scale - HR-MDS Cohort ECOG PS = 1 | 2 Participants |
| ECOG PS Scale - HR-MDS Cohort ECOG PS = 2 | 0 Participants |
| ECOG PS Scale - HR-MDS Cohort ECOG PS = 3 | 0 Participants |
| ECOG PS Scale - Other Cohort ECOG PS = 0 | 2 Participants |
| ECOG PS Scale - Other Cohort ECOG PS = 1 | 2 Participants |
| ECOG PS Scale - Other Cohort ECOG PS = 2 | 0 Participants |
| ECOG PS Scale - Other Cohort ECOG PS = 3 | 0 Participants |
| European Leukemia Net (ELN) Risk Stratification Criteria Adverse Risk | 14 Participants |
| European Leukemia Net (ELN) Risk Stratification Criteria Favorable Risk | 1 Participants |
| European Leukemia Net (ELN) Risk Stratification Criteria Intermediate Risk | 6 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 7 Participants |
| Race/Ethnicity, Customized White | 4 Participants |
| Region of Enrollment United States | 31 Participants |
| Revised International Prognostic Scoring System (IPSS-R) Risk Category High-risk: 4.5 - 6 | 1 Participants |
| Revised International Prognostic Scoring System (IPSS-R) Risk Category Intermediate-risk: 3 - 4.5 | 0 Participants |
| Revised International Prognostic Scoring System (IPSS-R) Risk Category Low-risk: 1.5 - 3 | 0 Participants |
| Revised International Prognostic Scoring System (IPSS-R) Risk Category Very high-risk: >6 | 5 Participants |
| Revised International Prognostic Scoring System (IPSS-R) Risk Category Very low-risk: ≤1.5 | 0 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 10 Participants |
| Somatic mutations FLT3 ITD | 2 Participants |
| Somatic mutations IDH1 or IDH2 | 6 Participants |
| Somatic mutations N/KRAS | 4 Participants |
| Somatic mutations NPM1 | 1 Participants |
| Somatic mutations TP53 | 11 Participants |
| Somatic mutations - AML Cohort FLT3 ITD | 2 Participants |
| Somatic mutations - AML Cohort IDH1 or IDH2 | 6 Participants |
| Somatic mutations - AML Cohort N/KRAS | 4 Participants |
| Somatic mutations - AML Cohort NPM1 | 1 Participants |
| Somatic mutations - AML Cohort TP53 | 5 Participants |
| Somatic Mutations - HR-MDS Cohort FLT3 ITD | 0 Participants |
| Somatic Mutations - HR-MDS Cohort IDH1 or IDH2 | 0 Participants |
| Somatic Mutations - HR-MDS Cohort N/KRAS | 0 Participants |
| Somatic Mutations - HR-MDS Cohort NPM1 | 0 Participants |
| Somatic Mutations - HR-MDS Cohort TP53 | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 31 |
| other Total, other adverse events | 28 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays
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.
Time frame: Up to 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Decitabine/Venetoclax (Single Arm) | 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 |
| Decitabine/Venetoclax (Single Arm) | 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 |
| Decitabine/Venetoclax (Single Arm) | 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
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)
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.
Time frame: 3 months
Secondary
Event-free Survival (EFS)
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.
Time frame: Up to 12 months
Secondary
Infection Rate Requiring Hospitalization
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.
Time frame: Up to 12 months
Secondary
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)
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.
Time frame: Up to 3 months
Secondary
Post Baseline Transfusion Independence Rate
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.
Time frame: Up to 12 months
Secondary
Rate of Hospitalization
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.
Time frame: Up to 12 months
Post Hoc
Best Overall Response in Patients With AML Based on ITT Analysis
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT Analysis | CR | 10 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT Analysis | CRi | 1 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT Analysis | MLFS | 1 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT Analysis | No Response | 9 Participants |
Post Hoc
Best Overall Response in Patients With AML Based on 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT-PP Analysis | CR | 10 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT-PP Analysis | CRi | 1 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT-PP Analysis | MLFS | 1 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With AML Based on ITT-PP Analysis | No Response | 7 Participants |
Post Hoc
Best Overall Response in Patients With HR-MDS
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With HR-MDS | CR | 3 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With HR-MDS | mCR | 1 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With HR-MDS | CRi | 2 Participants |
| Decitabine/Venetoclax (Single Arm) | Best Overall Response in Patients With HR-MDS | No Response | 0 Participants |
Post Hoc
Duration of Response (DOR) in AML Patients
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Duration of Response (DOR) in AML Patients | 5.5 months |
Post Hoc
Duration of Response (DOR) in HR-MDS Patients
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Duration of Response (DOR) in HR-MDS Patients | 5.2 months |
Post Hoc
Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT | 9 Participants |
Post Hoc
Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT-PP
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Measurable Residual Disease (MRD) in AML Patients Analyzed by ITT-PP | 9 Participants |
Post Hoc
Measurable Residual Disease (MRD) in HR-MDS Patients
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Measurable Residual Disease (MRD) in HR-MDS Patients | 4 Participants |
Post Hoc
Mortality
Mortality at 8 weeks was assessed for the 31 patients who were evaluated as part of the Primary Outcome Measure
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Mortality | 0 Participants |
Post Hoc
Overall Response Rate in Patients With AML by Intention-to-treat Per Protocol (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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Overall Response Rate in Patients With AML by Intention-to-treat Per Protocol (ITT-PP) Analysis | 12 Participants |
Post Hoc
Overall Response Rate in Patients With HR-MDS
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Overall Response Rate in Patients With HR-MDS | 4 Participants |
Post Hoc
Overall Response Rate (ORR) in Patients With AML by Intention-to-treat (ITT) Analysis
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Overall Response Rate (ORR) in Patients With AML by Intention-to-treat (ITT) Analysis | 12 Participants |
Post Hoc
Overall Survival in HR-MDS Patients
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Overall Survival in HR-MDS Patients | 9.6 months |
Post Hoc
Overall Survival (OS) in AML Patients
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine/Venetoclax (Single Arm) | Overall Survival (OS) in AML Patients | 16.1 months |