Working... Menu

NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01370213
Recruitment Status : Unknown
Verified March 2016 by Masonic Cancer Center, University of Minnesota.
Recruitment status was:  Active, not recruiting
First Posted : June 9, 2011
Last Update Posted : March 25, 2016
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE June 8, 2011
First Posted Date  ICMJE June 9, 2011
Last Update Posted Date March 25, 2016
Study Start Date  ICMJE September 2011
Estimated Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2011)
Rate of Donor Neutrophil Engraftment [ Time Frame: Day 28 ]
The rate of donor neutrophil engraftment in the absence of leukemia at day +28 will be determined. Successful neutrophil engraftment is defined as an absolute donor-derived neutrophil count of >500 cells/μl. Leukemia free is defined as <5% bone marrow blasts, absence of blasts with Auer rods; absence of extramedullary disease; but cytogenetic or molecular minimal residual disease is allowed.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01370213 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2012)
  • Disease Free Survival [ Time Frame: At 6 Months ]
  • Treatment Related Mortality (TRM) [ Time Frame: At 6 Months ]
    Cumulative incidence will be used to estimate TRM.
  • Incidence of Relapse [ Time Frame: 2 Years ]
    Cumulative incidence will be used to estimate relapse.
  • Rate of Early In Vivo Expansion of Natural Killer (NK) Cells [ Time Frame: Day 0 ]
    Successful in vivo donor NK cell expansion will be defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/μl in patient's peripheral blood 12 days after infusion.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2011)
  • Disease Free Survival [ Time Frame: At 6 Months ]
  • Treatment Related Mortality (TRM) [ Time Frame: At 6 Months ]
    Cumulative incidence will be used to estimate TRM.
  • Incidence of Relapse [ Time Frame: 2 Years ]
    Cumulative incidence will be used to estimate relapse.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
Descriptive Information
Brief Title  ICMJE NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases
Official Title  ICMJE Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases
Brief Summary This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. If 9 or more of these first 15 patients achieve leukemia free neutrophil engraftment at day +28 accrual will move to stage 2. In stage 2, an additional 28 patients will be enrolled for a total of 43 patients. Patients will be followed for disease response for 2 years.
Detailed Description A reduced intensity conditioning using Fludara, Cytoxan, and irradiation will start on day -22, followed by infusion of donor NK (natural killer) cells on day-17, 6 doses of interleukin-2 (IL-2) to promote NK expansion (day -17 to day -7), 2 doses of ATG for additional immunosuppression to promote engraftment (day -5 to -4), and infusion of a TCR α/β-depleted same donor graft on day 0.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: Preparative Regimen

    Preparative Regimen:

    1) fludarabine 40 mg/m^2 x 4 doses on Days -22 through -19 pretransplant, 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pretransplant, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pretransplant,

    Other Names:
    • Fludara
    • Cytoxan
    • radiation
  • Biological: NK Cells
    CD3^- CD19^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pretransplant.
    Other Name: Natural Killer cells
  • Drug: Interleukin-2
    Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion
    Other Name: IL-2
  • Biological: Anti-thymocyte globulin
    rabbit anti-thymocyte globulin will be administered on day -5 (0.5 mg/kg) and day -4 (2.5 mg/kg) pretransplant per institutional guidelines
    Other Name: ATG
  • Biological: Donor TCR α/β-depleted Cells
    Single donor TCR α/β-depleted filgrastim-mobilized peripheral blood stem cells (PBSC) graft (minimum cell dose of 5 x 10^6/kg) on day 0
    Other Name: stem cell graft
Study Arms Experimental: High-Risk Acute Myeloid Disease
Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and same donor TCR α/β-depleted cells infusion.
  • Drug: Preparative Regimen
  • Biological: NK Cells
  • Drug: Interleukin-2
  • Biological: Anti-thymocyte globulin
  • Biological: Donor TCR α/β-depleted Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: March 24, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2011)
Estimated Study Completion Date January 2019
Estimated Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

RAEB-1 or RAEB-2 fitting within one of the following disease groups:

  • Primary induction failure (PIF): Patients who have not achieved a complete remission (CR) after two induction cycles of cytotoxic therapy (i.e. 7+ 3, MEC, FLAG, etc.) and having ≤ 10,000 absolute circulating blasts measured at least 21 days from prior therapy. Hydroxyurea may be used to control blasts count. Demethylating agents do not count as induction therapy; however early re-induction therapy based on residual disease on a day 14 BM will count as a 2nd cycle
  • Relapsed Disease with low disease burden (AML or MDS with ≤ 10,000 absolute circulating blasts. No re-induction attempts are required, but a maximum of 2 reinduction attempts are allowed to be eligible.
  • CR3 or greater: This will include CRp defined as CR without platelet recovery to 100,000/mcL.
  • CR1 or CR2 with high risk features: Includes therapy induced, prior MDS or MPD, high risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated adult)

Patients with known prior central nervous system (CNS) involvement are eligible provided that it has been treated and CSF is clear for at least 2 weeks prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.

  • Available related HLA-haploidentical adult donor by at least Class I serologic typing at the A&B locus
  • Karnofsky score > 50%
  • Adequate organ function within 28 days of study registration defined as:

    • Hepatic: AST ≤ 3 x upper limit of institutional normal, total bilirubin ≤ 2.0 mg/dl
    • Renal: estimated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m^2
    • Pulmonary: Oxygen saturation ≥ 90% on room air and DLCOcor ≥ 40%
    • Cardiac: Ejection Fraction ≥ 35% and no uncontrolled angina, severe uncontrolled ventricular or arterial arrhythmias, or any evidence of acute ischemia or active conduction system abnormalities (rate controlled atrial fibrillation is not an exclusion)
  • Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (except for those prescribed as part of the study)
  • Women of child bearing potential must have a negative pregnancy test within 28 days prior to study registration and agree to use adequate birth control during study treatment
  • Voluntary written consent

Exclusion Criteria:

  • Biphenotypic leukemia
  • Allogeneic transplant for AML within previous 6 months
  • New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
  • Uncontrolled bacterial, fungal or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed
  • Known hypersensitivity to any of the study agents
  • Received any investigational drugs within the 14 days before 1st dose of fludarabine
  • Requires agents other than hydroxyurea to control blast count

Donor Selection:

  • Related donor (sibling, parent, offspring, parent or offspring of an HLA identical sibling) 12-75 years of age. (It is recognized individual institutions may have differing donor age guidelines. This is acceptable as long as no donor is younger than 12 years or older than 75 years).
  • Body weight of at least 40 kilograms
  • In general good health as determined by the medical provider
  • HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus
  • Able and willing to have up to 4 separate apheresis collections
  • Not pregnant
  • Voluntary written consent
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01370213
Other Study ID Numbers  ICMJE 2011LS027
MT2011-05 ( Other Identifier: Blood and Bone Marrow Transplant Program )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sarah Cooley, M.D. Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP