Vorinostat in Treating Patients With Acute Myeloid Leukemia
|Adult Acute Erythroid Leukemia (M6) Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Acute Promyelocytic Leukemia (M3) Recurrent Adult Acute Myeloid Leukemia Refractory Cytopenia With Multilineage Dysplasia Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: vorinostat||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Acute Myeloid Leukemia (AML)|
- Confirmed Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
The confirmed complete response rate was estimated by the number of participants with CR divided by the total number of evaluable participants.
According to the International Working Group (IWG) Criteria for response in AML, to be considered a CR, the following must be met for at least 4 weeks: ANC > 1500/mL, platelets > 100000/mL, no circulating blasts, bone marrow cellularity >20% (biopsy), trilineage maturation, < 5% bone marrow blasts, no auer rods and no extramedullary disease.
- Time to Progression (TTP) [ Time Frame: Duration of study (up to 2 years) ]Time to Progression (TTP) for each patient will be calculated as the number of days from date of registration to either date when disease progression was documented or date of last evaluation without disease progression. The TTP distribution will be estimated using the method of Kaplan-Meier
- Overall Survival (OS) [ Time Frame: Duration of study (up to 2 years) ]Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
- Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events [ Time Frame: Duration of study (up to 2 years) ]
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
Description of Grades:
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death
- Time to Treatment Failure (TTF) [ Time Frame: Duration of treatment (up to 17 cycles) ]Time to treatment failure (TTF) was defined as the time from registration to until the date of treatment discontinuation of any reason. Patients receiving treatment at the time of analysis were considered censored. The median TTF with 95% CI was estimated using the Kaplan Meier method.
|Study Start Date:||January 2006|
|Study Completion Date:||January 2010|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm I (once daily vorinostat)
Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Given orally once daily
Experimental: Arm II (thrice daily vorinostat)
Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Given orally three times daily
I. Determine the toxicity and the proportion of complete remissions associated with two different treatment schedules of vorinostat (SAHA) in patients with acute myeloid leukemia.
I. Determine the toxic effects of SAHA in this study population. II. Examine for preliminary evidence of re-expression of silenced genes in leukemic blasts in response to SAHA.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease status (relapsed vs untreated). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral vorinostat (SAHA) once a day on days 1-21. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oral SAHA three times a day on days 1-14. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 2 years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305773
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Steven Gore||Mayo Clinic|