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Myelodysplastic SyndromePhase 2NCT01593670

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

A Phase 2 study testing Decitabine, Vorinostat and Interleukin-2 in people with Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Myelodysplastic Syndrome
What is being tested?
Decitabine, Vorinostat and Interleukin-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
Mar 2013to 23 Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Mayo Clinic

    Rochester, Minnesota, 55901

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Decitabine, Vorinostat, Interleukin-2, Natural killer (NK) cells
Keywords
high risk myelodysplastic syndrome, natural killer cells
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

    Also called Dacogen

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

  • VorinostatDrug

    Also called Zolinza

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

  • Interleukin-2Biological

    Also called IL-2

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

  • Natural killer (NK) cellsOther

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

Study groups in NCT01593670
Study groupRoleWhat they receive
Patients With High Risk MDSExperimentalPatients 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.
Receives: Drug: Decitabine; Drug: Vorinostat; Biological: Interleukin-2; Other: Natural killer (NK) cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: After 2 Courses of Treatment (Approx. 3 months)

Secondary outcomes (4)

  1. 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.

    Measured: Day 1 through Month 3

  2. Number of Patients Who Became Transfusion Independent

    Measured: 4-6 Months Post Start of Cycle 1

  3. 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.

    Measured: After Cycle 2 (approx. 3 months)

  4. Overall Survival

    Patients alive at 1 year.

    Measured: 1 Year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2012 (estimated)
  2. Study startMar 2013
  3. Primary completion23 Oct 2018
  4. Study completion23 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01593670
Sponsor's protocol ID
2011LS124
Other IDs
MT2012-04
Status last verified
May 2019
First submitted
4 May 2012
Last updated
21 May 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Decitabine, Vorinostat and Interleukin-2 in people with Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of Patients Who Achieved a Clinical Response (time frame: After 2 Courses of Treatment (Approx. 3 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01593670.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.

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