Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
Myelodysplastic Syndrome
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring high risk myelodysplastic syndrome, natural killer cells
Eligibility Criteria
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
Sites / Locations
- Masonic Cancer Center, University of Minnesota
- Mayo Clinic
Arms of the Study
Arm 1
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.