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

NCT01593670 | Completed Phase 2 Results DMC

• 2 other identifiers: 2011LS124MT2012-04
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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.

Conditions

Myelodysplastic Syndrome

Keywords

high risk myelodysplastic syndrome; natural killer cells

Outcome Measures

Primary Outcomes (1)

• The Number of Patients Who Achieved a Clinical Response

  Clinical response includes: Complete Response (less than 5% myeloblasts present in the bone marrow and in the peripheral blood a hemoglobin of at least 11g/dl, platelets of at least 100 X 10E9/L, neutrophils of at least 1.0 X 10E9/L, and blasts 0%); Partial Response (all Complete Response criteria if previously abnormal except bone marrow myeloblasts are decreased by more than 50% over pre-treatment, but still greater than 5%); and hematologic improvement (a hemoglobin increase of greater than 1.5g/dl or decreased red blood cell transfusions by at least 4 per 8 week period, a platelet increase of more than 30 X 10E9/L for patients with a baseline of more than 20 X 10E9/L or an increase by 100% for those with a baseline of less than 20 X 10E9/L, and a neutrophil increase of at least 100% and an absolute increase of greater than 0.5 X 10E9/L.

  After 2 Courses of Treatment (Approx. 3 months)

Secondary Outcomes (4)

• Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events

  Day 1 through Month 3

• Number of Patients Who Became Transfusion Independent

  4-6 Months Post Start of Cycle 1

• Number of Patients Who Had Natural Killer (NK) Cell Expansion

  After Cycle 2 (approx. 3 months)

• Overall Survival

  1 Year

Study Arms (1)

Patients With High Risk MDS

EXPERIMENTAL

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.

Drug: Decitabine; Drug: Vorinostat; Biological: Interleukin-2; Other: Natural killer (NK) cells

Interventions

Decitabine DRUG

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

Also known as: Dacogen

Patients With High Risk MDS

Vorinostat DRUG

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

Also known as: Zolinza

Patients With High Risk MDS

Interleukin-2 BIOLOGICAL

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

Also known as: IL-2

Patients With High Risk MDS

Natural killer (NK) cells OTHER

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

Patients With High Risk MDS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Mayo Clinic: collaborator

Study Sites (2)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Decitabine; Vorinostat; Interleukin-2; Cell Count

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Results Point of Contact

• Title: Dr. Erica Warlick
• Organization: Masonic Cancer Center, University of Minnesota

ewarlick@umn.edu

612-625-5467

Study Officials

• Erica Warlick, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2012
• First Posted: May 8, 2012
• Study Start: March 1, 2013
• Primary Completion: October 23, 2018
• Study Completion: October 23, 2018
• Last Updated: May 21, 2019
• Results First Posted: June 14, 2017

Record last verified: 2019-05

Locations

US (2)