Clinical trial NCT01593670: Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Keywords: high risk myelodysplastic syndrome
natural killer cells
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
First posted: 2012-05-08
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

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

Primary outcomes:
measure: The Number of Patients Who Achieved a Clinical Response
timeFrame: After 2 Courses of Treatment (Approx. 3 months)
Secondary outcomes:
measure: Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events
timeFrame: Day 1 through Month 3
measure: Number of Patients Who Became Transfusion Independent
timeFrame: 4-6 Months Post Start of Cycle 1
measure: Number of Patients Who Had Natural Killer (NK) Cell Expansion
timeFrame: After Cycle 2 (approx. 3 months)
measure: Overall Survival
timeFrame: 1 Year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Erica Warlick, M.D.
role: PRINCIPAL_INVESTIGATOR
References: