Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT01593670|
Recruitment Status : Completed
First Posted : May 8, 2012
Results First Posted : June 14, 2017
Last Update Posted : May 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndrome||Drug: Decitabine Drug: Vorinostat Biological: Interleukin-2 Other: Natural killer (NK) cells||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Decitabine and Vorinostat With CD3/CD19 Depleted Haploidentical Donor Natural Killer (NK) Cells for the Treatment of High Risk Myelodysplastic Syndromes (MDS)|
|Study Start Date :||March 2013|
|Actual Primary Completion Date :||October 23, 2018|
|Actual Study Completion Date :||October 23, 2018|
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: Dacogen
200 mg by mouth (PO) twice a day on days 6-15
Other Name: Zolinza
6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17
Other Name: IL-2
Other: Natural killer (NK) cells
infusion intravenously (IV) over 15 to 60 minutes day 17
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|