Chemotherapy and a Donor Natural Killer Cell Infusion in Treating Patients With Relapsed or Persistent Leukemia or Myelodysplastic Syndrome After a Donor Stem Cell Transplant
The goal of this study is to see if there is a benefit to giving chemotherapy and then natural killer (NK) cells. The NK cells must come from a family member who shares half of the patients HLA proteins. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body.
Patients whose blood cancer is not cured with a stem cell transplant do not have standard treatment options. Studies have shown that NK cells from a donor can be given safely and can be helpful in treating some blood diseases. These NK cells are collected from the patients donor and purified using a separation system called CliniMACS that has been used safely in previous studies and is used in this study with the approval of the Federal Food and Drug Administration. The researchers want to find out what effects the NK cells will have on blood cancer and bone marrow function and how to maximize its benefits in treating blood cancers. The researchers hope that giving chemotherapy and then NK cells will be a better treatment for the disease than the current available treatment options.
Funding Source - Food and Drug Administration/Office of Orphan Products Development
Biological: natural killer cell therapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of HLA Haploidentical Natural Killer Cell Infusion for Treatment of Relapsed or Persistent Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant|
- Disease-free survival one year after NK cell infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Achievement of complete or partial remission at one year following NK infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: natural killer (NK) cells with salvage chemotherapy
This is a Phase II study, designed to determine the efficacy of natural killer (NK) cells isolated from HLA-haploidentical related donors when infused following a salvage chemotherapy regimen into patients who have relapsed or persistent leukemia following an allogeneic HLA-compatible HSCT and who are ineligible for a second HSCT.
Biological: natural killer cell therapy
The patient must be admitted by Day -8 to the Bone Marrow Transplant Service. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor and will be monitored for hematopoietic recovery.Drug: cyclophosphamide
Day -6 cyclophosphamide 60mg/kg infused over 1 hour (dose adjusted for body weight) for 2 daysDrug: fludarabine
Day -5 fludarabine 25mg/m2 CIV for 5 days
- Determine the anti-leukemic efficacy of allogeneic HLA-haploidentical related natural killer (NK) cell infusion following a cytoreductive regimen with cyclophosphamide and fludarabine in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic CML who have relapsed following allogeneic hematopoietic stem cell transplant, where efficacy is defined as the achievement of complete or partial remission at one year following NK cell infusion.
- To assess treatment efficacy, as defined by achievement of complete or partial remission, at 3 and 6 months following HLA-haploidentical related NK cell infusion.
- To assess the effects of an HLA-haploidentical related NK cell infusion on the sustained engraftment and recovery of an HLA-matched stem cell allograft.
- To assess the risk of inducing graft-vs-host disease (GVHD) or altering its severity.
- To provide preliminary evidence that specific donor KIR-recipient HLA ligand combinations relating to missing self-MHC class I ligand or missing class I ligand are associated with higher NK alloreactivity and improved outcome.
- To monitor the extent and duration of NK cell donor chimerism.
- To monitor NK cell reconstitution through NK receptor cell surface phenotyping (CD94/NKG2A, ILT-2, KIR expression) and function (intracellular IFN-γ, cytotoxicity) on day 15, 30, 60, 100, and 200 following the NK infusion and to correlate with outcome.
- To correlate the magnitude of NK effect with disease and known survival risk factors (time from allogeneic HSCT to relapse; < 6 months vs > 6 months).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00526292
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Katherine Hsu, MD, PhD||Memorial Sloan Kettering Cancer Center.|
|Principal Investigator:||Ann Alice Jakubowski, MD, PhD||Memorial Sloan Kettering Cancer Center.|