Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes

NCT ID: NCT01593670

Last Updated: 2019-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2018-10-23

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.

Conditions

Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5.

Vorinostat

Intervention Type: DRUG

200 mg by mouth (PO) twice a day on days 6-15

Interleukin-2

Intervention Type: BIOLOGICAL

6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17

Natural killer (NK) cells

Intervention Type: OTHER

infusion intravenously (IV) over 15 to 60 minutes day 17

Interventions

Decitabine

administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5.

Intervention Type: DRUG

Vorinostat

200 mg by mouth (PO) twice a day on days 6-15

Intervention Type: DRUG

Interleukin-2

6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17

Intervention Type: BIOLOGICAL

Natural killer (NK) cells

infusion intravenously (IV) over 15 to 60 minutes day 17

Intervention Type: OTHER

Other Intervention Names

Dacogen; Zolinza; IL-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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erica Warlick, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MT2012-04

Identifier Type: OTHER

Identifier Source: secondary_id

2011LS124

Identifier Type: -

Identifier Source: org_study_id