This trial is active, not recruiting.

Condition myelodysplastic syndrome
Treatments decitabine, vorinostat, interleukin-2, natural killer (nk) cells
Phase phase 2
Target HDAC
Sponsor Masonic Cancer Center, University of Minnesota
Collaborator Mayo Clinic
Start date March 2013
End date October 2015
Trial size 9 participants
Trial identifier NCT01593670, 2011LS124, MT2012-04


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
decitabine Dacogen
administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5.
vorinostat Zolinza
200 mg by mouth (PO) twice a day on days 6-15
interleukin-2 IL-2
6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17
natural killer (nk) cells
infusion intravenously (IV) over 15 to 60 minutes day 17

Primary Outcomes

Objective Response Rate
time frame: After 2 Courses of Treatment (Approx. 3 months)

Secondary Outcomes

Safety and Tolerability
time frame: Day 1 through Month 3
Number of Patients Who Became Transfusion Independent
time frame: 4-6 Months Post Start of Cycle 1
Natural Killer Cell Expansion
time frame: After Cycle 2 (approx. 3 months)
Overall Survival
time frame: 1 Year

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: - Diagnosis of high risk myelodysplastic (MDS) that meets one of the following disease classifications and is requiring treatment: - International Prognostic Scoring System (IPSS) Category: INT-2 or High Risk - WHO Classification: RAEB-1 or RAEB-2 - High risk cytogenetic abnormality as defined by presence of Monosomy 7, complex karytope, or monosomal karyotype - WHO Based Prognostic Scoring System (WPSS): High or Very High Risk - Patients may be untreated or have had a maximum of 2 cycles of hypomethylating agents (azacitidine or decitabine) without evidence of treatment failure as defined by progression to more advanced MDS Who classification or AML. Patients must not have received treatment for their MDS within 4 weeks of beginning the trial. Treatments allowed prior to that time include azacitidine or decitabine and hematopoietic growth factors. No prior AML-like induction therapy allowed. - Age ≥ 18 years of age - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Available related HLA-haploidentical NK cell donor by at least Class I serologic typing at the A&B locus - Have acceptable organ function within 14 days of enrollment - Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the natural killer (NK) cell infusion - Women of child bearing potential must agree to use effective methods of contraception - Voluntary written consent Exclusion Criteria: - Pregnant or lactating. - Prior 7 + 3 (cytarabine given continuously for 7 days with an anthracycline drug, such as daunorubicin or idarubicin given for the 1st 3 days of treatment) or other AML-type induction chemotherapy - New progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan that has not been evaluated with bronchoscopy (when feasible) - Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is allowed - Pleural effusion moderate to large in size that are detectable on chest xray - Known hypersensitivity to one or more of the study agents - Prior hypomethylating treatment greater than 2 cycles or with documented treatment failure - Prior use of histone deacetylase inhibitors - Serious medical or psychiatric illness likely to interfere with participation in this clinical study in the opinion of the enrolling investigator - Inability to swallow capsules - Active human immunodeficiency virus (HIV) - Other active and potentially life threatening malignancy excluding localized basal or squamous cell skin cancer, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer

Additional Information

Official title Decitabine and Vorinostat With CD3/CD19 Depleted Haploidentical Donor Natural Killer (NK) Cells for the Treatment of High Risk Myelodysplastic Syndromes (MDS)
Principal investigator Erica Warlick, M.D.
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota.