Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
This is a Phase II therapeutic trial combining Decitabine days 1-5 with oral Vorinostat twice daily days 6-15 followed by a single infusion of CD3-/CD19- enriched donor natural killer (NK) cells on day 17 and a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion. Two courses of treatment will be given separated by 6-8 weeks. The intent is to administer all treatment in the outpatient setting.
Other: Natural killer (NK) cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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)|
- Objective Response Rate [ Time Frame: After 2 Courses of Treatment (Approx. 3 months) ] [ Designated as safety issue: No ]Defined as Complete response (CR) + partial response (PR) + hematologic improvement (HI).
- Safety and Tolerability [ Time Frame: Day 1 through Month 3 ] [ Designated as safety issue: Yes ]Assess the safety and tolerability of Decitabine and Vorinostat followed by an infusion of CD3-/CD19-donor natural killer (NK) cells and a short course of IL-2 when given in the outpatient setting in patients with high risk myelodysplastic syndrome (MDS).
- Number of Patients Who Became Transfusion Independent [ Time Frame: 4-6 Months Post Start of Cycle 1 ] [ Designated as safety issue: No ]
- Natural Killer Cell Expansion [ Time Frame: After Cycle 2 (approx. 3 months) ] [ Designated as safety issue: No ]Defined as patients with in vivo expansion.
- Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]Patients alive at 1 year.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2017 (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|