Clinical trial NCT00526292
Conditions: Leukemia Myelodysplastic Syndromes
Keywords: recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia blastic phase chronic myelogenous leukemia previously treated myelodysplastic syndromes childhood myelodysplastic syndromes recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia childhood chronic myelogenous leukemia relapsing chronic myelogenous leukemia adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22)
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2007-08-01; Completion date: 2015-07-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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

Detailed description:
OBJECTIVES:

Primary

* 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.

Secondary

* 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).

Arms: arm 1: 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.
Interventions: intervention 1: natural killer cell therapy intervention 2: cyclophosphamide intervention 3: fludarabine
Intervention descriptions: intervention 1: 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. intervention 2: Day -6 cyclophosphamide 60mg/kg infused over 1 hour (dose adjusted for body weight) for 2 days intervention 3: Day -5 fludarabine 25mg/m2 CIV for 5 days

Protocol documents: