search
Back to results

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

Primary Purpose

Myelodysplastic Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Decitabine
Vorinostat
Interleukin-2
Natural killer (NK) cells
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring high risk myelodysplastic syndrome, natural killer cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Arm Label

Patients With High Risk MDS

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events
Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event.
Number of Patients Who Became Transfusion Independent
Number of Patients Who Had Natural Killer (NK) Cell Expansion
NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion.
Overall Survival
Patients alive at 1 year.

Full Information

First Posted
May 4, 2012
Last Updated
May 14, 2019
Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Mayo Clinic
search

1. Study Identification

Unique Protocol Identification Number
NCT01593670
Brief Title
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

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
October 23, 2018 (Actual)
Study Completion Date
October 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Mayo Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
high risk myelodysplastic syndrome, natural killer cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients With High Risk MDS
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
Zolinza
Intervention Description
200 mg by mouth (PO) twice a day on days 6-15
Intervention Type
Biological
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2
Intervention Description
6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17
Intervention Type
Other
Intervention Name(s)
Natural killer (NK) cells
Intervention Description
infusion intravenously (IV) over 15 to 60 minutes day 17
Primary Outcome Measure Information:
Title
The Number of Patients Who Achieved a Clinical Response
Description
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.
Time Frame
After 2 Courses of Treatment (Approx. 3 months)
Secondary Outcome Measure Information:
Title
Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events
Description
Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event.
Time Frame
Day 1 through Month 3
Title
Number of Patients Who Became Transfusion Independent
Time Frame
4-6 Months Post Start of Cycle 1
Title
Number of Patients Who Had Natural Killer (NK) Cell Expansion
Description
NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion.
Time Frame
After Cycle 2 (approx. 3 months)
Title
Overall Survival
Description
Patients alive at 1 year.
Time Frame
1 Year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erica Warlick, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55901
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs