Brief Summary
This is a Phase 1b, open-label study evaluating Venetoclax in combination with intensive induction and consolidation chemotherapy in previously untreated, adult patients with acute myeloid leukemia. In Part 1, the dose escalation phase, the safety and tolerability of the combination with Venetoclax at different doses and duration will inform the appropriate dose(s) and regimen(s) for Part 2. In Part 2, the dose expansion phase, a maximum of 28 additional patients will be randomized 1:1 to the MTD determined in Part 1 and the starting dose (assuming the MTD is not the starting dose), to further evaluate the safety and efficacy of the study drug combination.
Brief Title
Venetoclax Plus Intensive Chemotherapy in AML and Advanced MDS
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability and determine the dose-limiting toxicity and the maximum tolerated dose (MTD) of the combination of daunorubicin \& cytarabine chemotherapy plus Venetoclax for patients with AML
SECONDARY OBJECTIVES:
I. To assess efficacy by response per 2022 ELN and revised International Working Group (IWG) criteria.
II. To determine additional response parameters: CR/CRi and CR/CRh rates.
III. To determine time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR)
EXPLORATORY OBJECTIVES:
I. To assess rates of LSC eradication by means of MFC and single cell sequencing, as well as a novel assay that uses an extended leukemia-specific NGS panel for measuring MRD in cfDNA and BM ("high resolution MRD assay")
II. To comprehensively analyze the clonal architectural and transcriptomic shifts in residual LSC under therapy
III. To determine the protein expression of BCL-2 family members and the reliance of leukemic cells on differing members of the BH3 family at the time of diagnosis and relapse and explore association of such observations with response to Venetoclax when combined with chemotherapy
Dose Escalation Cohorts:
A minimum of 3 patients will be treated in each cohort (dose level) sequentially in a 3+3 design. Patients will receive the Venetoclax plus daunorubicin/cytarabine combination as shown below
Patients aged ≤ 60 years
Cohort 1A:
Daunorubicin 60mg/m2 intravenously (IV) daily on days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 2A:
Daunorubicin 90mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 3A:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-11
Cohort 4A:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-14
Note: No DLTs in induction phase have been observed and Cohort 3A has completed enrollment. However, the daunorubicin dose of 90mg/m2 will not be further studied due to recently reported results of no superiority over the dose of 60mg/m2.
Patients \>60 years
Cohort 1B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 2B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Day 3-11
Cohort 3B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-14
Expansion Cohort(s):
A maximum of 28 additional patients aged ≤ 60 years and 28 patients \>60 years will be randomized (1:1) to the MTD the starting dose (assuming the MTD is not the starting dose), to further evaluate safety and efficacy of the study drug combination and identify the optimal phase 2 dose.
Consolidation Phase:
Patients who achieve CRc post induction will proceed to consolidation therapy with high-dose cytarabine in combination with escalating doses of Venetoclax. The 3+3 algorithm will be applied for dose escalation/de-escalation of Venetoclax in combination with Cytarabine. As of February 2023, there have been 2/6 hematologic DLTs in consolidation cohort 1B, therefore we will no longer give Venetoclax in combination with high-dose cytarabine during the consolidation phase, in pts \>60 yrs of age. We will also not explore dose escalation of Venetoclax during consolidation in the 60-year-old or younger age-group before RP2D of induction is determined. All subjects ≤ 60yrs will be treated at the consolidation Cohort 1A dose.
In the expansion phase, Venetoclax, at the dose of 200mg daily, will be re-introduced in combination with chemotherapy, albeit at a shorter than a 7-day duration; the consolidation regimen for patients older than 60 years of age will consist of cytarabine at the dose of 0.5-1g/m2 every 12 hours on days 1,3,5 or days 1,2,3 (per ELN 2022 guidelines) plus Venetoclax 200mg for 5 days.
Patients ≤ 60 years
Consolidation cohort 1A:
Cytarabine 1.5g/m2 every 12 hours on Days 1, 3, 5 OR days 1, 2, 3; Venetoclax 200mg on Days 1-7
Patients \>60 years
Consolidation cohort 1B:
Cytarabine 0.5-1g/m2 every 12 hours on days 1, 3, 5 OR days 1, 2, 3; Venetoclax 200mg on Days 1-5
A minimum of 3 patients will be treated in each cohort (dose level) sequentially in a 3+3 design. Additional 3 subjects may be backfilled to lower dose levels so that each cohort will reach a total of 6 subjects. Once the MTD is reached, a maximum of 28 additional patients will be randomized 1:1 to the MTD or a dose level below the MTD the starting dose (assuming the MTD is not the starting dose) for a total of up to 20 patients (6 from Part 1, 20 from Part 2) treated at each of those dose levels. A maximum of 52 patients (including backfill and expansion cohorts) 60 years or younger and 46 patients older than 60 years may be enrolled in this Phase 1b study.
Patients will receive one cycle of induction chemotherapy as described above. An interim bone marrow evaluation will be performed between days 14-21 from chemotherapy initiation. Patients who will not achieve marrow hypoplasia (cellularity \<20% of which less than 5% are residual blasts) will receive a second induction, as allowed by their clinical circumstances. Second induction chemotherapy will be comprised of daunorubicin 60mg/m2 x 2 days (45mg/m2 x 2 days in patients initially treated with daunorubicin 90mg/m2) and cytarabine 100mg/m2 x 5 days along with Venetoclax 400mg for 7 days, whether younger or older than 60 years of age, and disease assessment will be performed on day 28 (up to day 42) of second induction. Patients who do not achieve CR/CRi after a second induction will be taken off protocol and will be treated per treating physician's discretion. Patients who achieve CRc will proceed to consolidation therapy with high-dose cytarabine in combination with escalating doses of Venetoclax (200-400mg) for up to four 28(-42)-day cycles, as described above (complete dose adjustment guidelines are outlined in the study protocol); consolidation with allogeneic transplantation off protocol is allowed per physician's discretion. The 3+3 algorithm will be applied for dose escalation/de-escalation of Venetoclax in combination with high-dose cytarabine. Each cycle of cytarabine will last up to 42 days.
All participants should undergo response evaluations between Day 28 and Day 42 of first and/or second induction course. Unless there is clear evidence of progressive disease in the blood, bone marrow aspiration is required and bone marrow biopsy is strongly encouraged. In cases with hypocellular marrows (\<10% cellularity), repeat bone marrow examinations should be considered when there is evidence of hematopoietic recovery. If multiple bone marrow examinations are performed, the last examination will be used to classify the patient's response. The final response will be determined no later than day 42 from the start of therapy.
I. To evaluate the safety and tolerability and determine the dose-limiting toxicity and the maximum tolerated dose (MTD) of the combination of daunorubicin \& cytarabine chemotherapy plus Venetoclax for patients with AML
SECONDARY OBJECTIVES:
I. To assess efficacy by response per 2022 ELN and revised International Working Group (IWG) criteria.
II. To determine additional response parameters: CR/CRi and CR/CRh rates.
III. To determine time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR)
EXPLORATORY OBJECTIVES:
I. To assess rates of LSC eradication by means of MFC and single cell sequencing, as well as a novel assay that uses an extended leukemia-specific NGS panel for measuring MRD in cfDNA and BM ("high resolution MRD assay")
II. To comprehensively analyze the clonal architectural and transcriptomic shifts in residual LSC under therapy
III. To determine the protein expression of BCL-2 family members and the reliance of leukemic cells on differing members of the BH3 family at the time of diagnosis and relapse and explore association of such observations with response to Venetoclax when combined with chemotherapy
Dose Escalation Cohorts:
A minimum of 3 patients will be treated in each cohort (dose level) sequentially in a 3+3 design. Patients will receive the Venetoclax plus daunorubicin/cytarabine combination as shown below
Patients aged ≤ 60 years
Cohort 1A:
Daunorubicin 60mg/m2 intravenously (IV) daily on days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 2A:
Daunorubicin 90mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 3A:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-11
Cohort 4A:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-14
Note: No DLTs in induction phase have been observed and Cohort 3A has completed enrollment. However, the daunorubicin dose of 90mg/m2 will not be further studied due to recently reported results of no superiority over the dose of 60mg/m2.
Patients \>60 years
Cohort 1B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-8
Cohort 2B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Day 3-11
Cohort 3B:
Daunorubicin 60mg/m2 IV daily on Days 2-4; Cytarabine 100mg/m2 IV daily on Days 2-8; Venetoclax 100mg orally on Day 1, 200mg on Day 2, 400mg on Days 3-14
Expansion Cohort(s):
A maximum of 28 additional patients aged ≤ 60 years and 28 patients \>60 years will be randomized (1:1) to the MTD the starting dose (assuming the MTD is not the starting dose), to further evaluate safety and efficacy of the study drug combination and identify the optimal phase 2 dose.
Consolidation Phase:
Patients who achieve CRc post induction will proceed to consolidation therapy with high-dose cytarabine in combination with escalating doses of Venetoclax. The 3+3 algorithm will be applied for dose escalation/de-escalation of Venetoclax in combination with Cytarabine. As of February 2023, there have been 2/6 hematologic DLTs in consolidation cohort 1B, therefore we will no longer give Venetoclax in combination with high-dose cytarabine during the consolidation phase, in pts \>60 yrs of age. We will also not explore dose escalation of Venetoclax during consolidation in the 60-year-old or younger age-group before RP2D of induction is determined. All subjects ≤ 60yrs will be treated at the consolidation Cohort 1A dose.
In the expansion phase, Venetoclax, at the dose of 200mg daily, will be re-introduced in combination with chemotherapy, albeit at a shorter than a 7-day duration; the consolidation regimen for patients older than 60 years of age will consist of cytarabine at the dose of 0.5-1g/m2 every 12 hours on days 1,3,5 or days 1,2,3 (per ELN 2022 guidelines) plus Venetoclax 200mg for 5 days.
Patients ≤ 60 years
Consolidation cohort 1A:
Cytarabine 1.5g/m2 every 12 hours on Days 1, 3, 5 OR days 1, 2, 3; Venetoclax 200mg on Days 1-7
Patients \>60 years
Consolidation cohort 1B:
Cytarabine 0.5-1g/m2 every 12 hours on days 1, 3, 5 OR days 1, 2, 3; Venetoclax 200mg on Days 1-5
A minimum of 3 patients will be treated in each cohort (dose level) sequentially in a 3+3 design. Additional 3 subjects may be backfilled to lower dose levels so that each cohort will reach a total of 6 subjects. Once the MTD is reached, a maximum of 28 additional patients will be randomized 1:1 to the MTD or a dose level below the MTD the starting dose (assuming the MTD is not the starting dose) for a total of up to 20 patients (6 from Part 1, 20 from Part 2) treated at each of those dose levels. A maximum of 52 patients (including backfill and expansion cohorts) 60 years or younger and 46 patients older than 60 years may be enrolled in this Phase 1b study.
Patients will receive one cycle of induction chemotherapy as described above. An interim bone marrow evaluation will be performed between days 14-21 from chemotherapy initiation. Patients who will not achieve marrow hypoplasia (cellularity \<20% of which less than 5% are residual blasts) will receive a second induction, as allowed by their clinical circumstances. Second induction chemotherapy will be comprised of daunorubicin 60mg/m2 x 2 days (45mg/m2 x 2 days in patients initially treated with daunorubicin 90mg/m2) and cytarabine 100mg/m2 x 5 days along with Venetoclax 400mg for 7 days, whether younger or older than 60 years of age, and disease assessment will be performed on day 28 (up to day 42) of second induction. Patients who do not achieve CR/CRi after a second induction will be taken off protocol and will be treated per treating physician's discretion. Patients who achieve CRc will proceed to consolidation therapy with high-dose cytarabine in combination with escalating doses of Venetoclax (200-400mg) for up to four 28(-42)-day cycles, as described above (complete dose adjustment guidelines are outlined in the study protocol); consolidation with allogeneic transplantation off protocol is allowed per physician's discretion. The 3+3 algorithm will be applied for dose escalation/de-escalation of Venetoclax in combination with high-dose cytarabine. Each cycle of cytarabine will last up to 42 days.
All participants should undergo response evaluations between Day 28 and Day 42 of first and/or second induction course. Unless there is clear evidence of progressive disease in the blood, bone marrow aspiration is required and bone marrow biopsy is strongly encouraged. In cases with hypocellular marrows (\<10% cellularity), repeat bone marrow examinations should be considered when there is evidence of hematopoietic recovery. If multiple bone marrow examinations are performed, the last examination will be used to classify the patient's response. The final response will be determined no later than day 42 from the start of therapy.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-920-4826
Central Contact Email
imantzar@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Eligibility Criteria
Inclusion Criteria:
* New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
* Patients ≥ 18 to ≤ 75 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
* Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
* Ability to understand and provide signed informed consent
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Exclusion Criteria:
* Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (FAB class M3-AML)
* Subject has known active CNS involvement with AML
* Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<45% by echocardiogram or multi-gated acquisition (MUGA) scan
* Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
* Patients with uncontrolled infection with human immunodeficiency virus (HIV) or active Hepatitis B or C
* Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally.
* Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.
* Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea and/or cytarabine (1 or 2 doses; up to 2 is permitted to meet this criterion.)
* Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).
* New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
* Patients ≥ 18 to ≤ 75 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
* Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
* Ability to understand and provide signed informed consent
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Exclusion Criteria:
* Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (FAB class M3-AML)
* Subject has known active CNS involvement with AML
* Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<45% by echocardiogram or multi-gated acquisition (MUGA) scan
* Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
* Patients with uncontrolled infection with human immunodeficiency virus (HIV) or active Hepatitis B or C
* Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally.
* Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.
* Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea and/or cytarabine (1 or 2 doses; up to 2 is permitted to meet this criterion.)
* Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).
Inclusion Criteria
Inclusion Criteria:
* New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
* Patients ≥ 18 to ≤ 75 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
* Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
* Ability to understand and provide signed informed consent
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
* New diagnosis of AML by WHO criteria. Patients with higher risk MDS (R-IPSS\>3.5) and 10% blasts or more, or proliferative (WBC ≥ 13 x 10⁹/L) CMML-2 are also eligible at the discretion of the PI. Patients having received any prior hypomethylating agent with or without BCL2 inhibitor therapy for MDS/AML are also eligible at the discretion of the PI
* Patients ≥ 18 to ≤ 75 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Adequate renal function including creatinine clearance \> 30 mL/min based on the Cockcroft Gault equation.
* Adequate hepatic function including total bilirubin \< 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement
* Ability to understand and provide signed informed consent
* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Gender
All
Gender Based
false
Keywords
AML
MDS
Venetoclax
Ven
7+3
daunorubicin and cytarabine
daunorubicin
cytarabine
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT05342584
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2021-13643
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Phase 1B Study of Venetoclax in Combination With Standard Intensive Chemotherapy With Daunorubicin Plus Cytarabine Followed by High-Dose Cytarabine in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia and Advanced Myelodysplastic Syndrome
Primary Outcomes
Outcome Description
To characterize the safety profile (incidence of AEs) and dose-limiting toxicities (DLTs) of Venetoclax in combination with Daunorubicin and Cytarabine
Outcome Measure
Frequency and severity of adverse events (AEs)
Outcome Time Frame
Through study completion, up to 6 years
Outcome Description
To determine a safe and tolerable dose of Venetoclax in combination with Daunorubicin and Cytarabine during induction
Outcome Measure
Maximum tolerated dose of Venetoclax in combination with Daunorubicin and Cytarabine
Outcome Time Frame
Through study completion, up to 6 years
Outcome Description
To determine a safe and tolerable dose of Venetoclax in combination high dose of Cytarabine during consolidation
Outcome Measure
Maximum tolerated dose of Venetoclax in combination with high dose cytarabine
Outcome Time Frame
Through study completion, up to 6 years
Secondary Outcomes
Outcome Description
Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.
Outcome Time Frame
Through study completion, up to 6 years
Outcome Measure
Overall response rate (ORR)
Outcome Description
Will be estimated along with the 95% credible interval
Outcome Time Frame
Through study completion, up to 6 years
Outcome Measure
Hematologic response rate
Outcome Description
Defined as the number of days from the date of initial response (CRi or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.
Outcome Time Frame
From the date of initial response, assessed up to 6 years
Outcome Measure
Duration of response
Outcome Description
Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Outcome Time Frame
Through study completion, up to 6 years
Outcome Measure
Overall survival
Outcome Description
Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Outcome Time Frame
Through study completion, up to 6 years
Outcome Measure
Event-free survival
Outcome Description
Will be estimated along with the 95% credible interval.
Outcome Time Frame
Through study completion, up to 6 years
Outcome Measure
Morphologic leukemia-free state
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org