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Decitabine and Vorinostat With CD3/CD19 Depleted Haploidentical Donor Natural Killer (NK) Cells for the Treatment of High Risk Myelodysplastic Syndromes (MDS)

Phase 2
18 Years
75 Years
Open (Enrolling)
Myelodysplastic Syndrome

Thank you

Trial Information

Decitabine and Vorinostat With CD3/CD19 Depleted Haploidentical Donor Natural Killer (NK) Cells for the Treatment of High Risk Myelodysplastic Syndromes (MDS)

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.

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 as defined below within 14 days (28 days for cardiac)
of enrollment:

- Renal: Creatinine: ≤ 2.0 mg/dL

- Hepatic: SGOT/SGPT < 5 x upper limit of institutional normal (ULN)

- Pulmonary: oxygen saturation ≥ 90% on room air

- Cardiac:Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or
multigated acquisition scan (MUGA) ≥ 40%, no uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. QTc < 500 msec

- Ability to be off prednisone and other immunosuppressive drugs for at least 3 days
prior to the natural killer (NK) cell infusion (excluding pre-meds)

- Women of child bearing potential must agree to use effective methods of contraception
(diaphragm, birth control pills, injections, intrauterine device [IUD], surgical
sterilization, subcutaneous implants, or abstinence, etc.) from the time of signing
the consent form and for 2 months after the last dose of chemotherapy.

- Voluntary written consent before performance of any study-related procedure not part
of normal medical care, with the understanding that consent may be withdrawn at any
time without prejudice to future medical care.

Exclusion Criteria:

- Pregnant or lactating. The agents used in this study are known to be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk.
Confirmation that the patient is not pregnant must be established by a negative
pregnancy test result obtained during screening. Pregnancy testing is not required
for surgically sterilized or post-menopausal women.

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response Rate

Outcome Description:

Defined as Complete response (CR) + partial response (PR) + hematologic improvement (HI).

Outcome Time Frame:

After 2 Courses of Treatment (Approx. 3 months)

Safety Issue:


Principal Investigator

Erica Warlick, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

June 2017

Related Keywords:

  • Myelodysplastic Syndrome
  • high risk myelodysplastic syndrome
  • natural killer cells
  • Myelodysplastic Syndromes
  • Preleukemia



Mayo Clinic Rochester, Minnesota  55905
Masonic Cancer Center, University of Minnesota Minneapolis, Minnesota  55455