Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
|Myelodysplastic Syndrome||Drug: Decitabine Drug: Vorinostat Biological: Interleukin-2 Other: Natural killer (NK) cells||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Decitabine and Vorinostat With CD3/CD19 Depleted Haploidentical Donor Natural Killer (NK) Cells for the Treatment of High Risk Myelodysplastic Syndromes (MDS)|
- The Number of Patients Who Achieved a Clinical Response [ Time Frame: After 2 Courses of Treatment (Approx. 3 months) ]Clinical response includes: Complete Response (less than 5% myeloblasts present in the bone marrow and in the peripheral blood a hemoglobin of at least 11g/dl, platelets of at least 100 X 10E9/L, neutrophils of at least 1.0 X 10E9/L, and blasts 0%); Partial Response (all Complete Response criteria if previously abnormal except bone marrow myeloblasts are decreased by more than 50% over pre-treatment, but still greater than 5%); and hematologic improvement (a hemoglobin increase of greater than 1.5g/dl or decreased red blood cell transfusions by at least 4 per 8 week period, a platelet increase of more than 30 X 10E9/L for patients with a baseline of more than 20 X 10E9/L or an increase by 100% for those with a baseline of less than 20 X 10E9/L, and a neutrophil increase of at least 100% and an absolute increase of greater than 0.5 X 10E9/L.
- Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events [ Time Frame: Day 1 through Month 3 ]Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event.
- Number of Patients Who Became Transfusion Independent [ Time Frame: 4-6 Months Post Start of Cycle 1 ]
- Number of Patients Who Had Natural Killer (NK) Cell Expansion [ Time Frame: After Cycle 2 (approx. 3 months) ]NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion.
- Overall Survival [ Time Frame: 1 Year ]Patients alive at 1 year.
|Study Start Date:||March 2013|
|Study Completion Date:||July 2016|
|Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Patients With High Risk MDS
Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date.
administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5.
Other Name: DacogenDrug: Vorinostat
200 mg by mouth (PO) twice a day on days 6-15
Other Name: ZolinzaBiological: Interleukin-2
6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17
Other Name: IL-2Other: Natural killer (NK) cells
infusion intravenously (IV) over 15 to 60 minutes day 17
A single donor apheresis will be collected on day 15 of cycle 1, enriched for NK cells with the large scale CliniMacs device (Miltenyi) and activated by overnight incubation with IL-2. After washing, the final NK cell product will be divided in two, with half given fresh on day 17 of course #1 and half stored frozen until day 17 of course #2.
Clinical response will be formally assessed 4-6 weeks after the start of 2nd course based on International Working Group (IWG) criteria; however, bone marrow evaluations will be completed to assess for any sign of significant disease progression between cycle 1 and 2.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01593670
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Rochester, Minnesota, United States, 55901|
|Principal Investigator:||Erica Warlick, M.D.||Masonic Cancer Center, University of Minnesota|