NK DLI in Patients After Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)
This is a phase I/II study of highly selected donor lymphocyte infusions in patients undergoing HLA-haploidentical hemopoietic stem cell transplantation. Patients will be offered "pre-emptive" NK-DLI early after HSCT.
Three schedules of NK-cell infusion will be studied: Basel patients (adult and pediatric) will receive NK-DLI on days +40 and +100 (pre-emptive-late); Frankfurt patients (pediatric) will receive NK-DLI on days +3, +40, and +100 (pre-emptive early). Patients not receiving pre-emptive NK-DLI with loss in donor chimerism or with evidence of minimal residual disease will be offered "therapeutic" NK-DLI.
|Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Myelodysplastic Syndromes Lymphoma Neuroblastoma Rhabdomyosarcoma||Biological: CD3-depleted/CD56+ selected natural killer cells collected from apheresis products||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Natural Killer Cell Selected T-cell Depleted Donor Lymphocyte Infusions (NK-DLI) in Patients After HLA-haploidentical Allogeneic Stem Cell Transplantation|
- Feasibility of NK-DLI production [ Time Frame: At day of transplant (day 0) ]The feasibility of the production of expanded NK-cell DLI will be measured. Primary quality measures of the NK cell product are the number of NK cells that can be produced (CD56+/cluster of differentiation 3(CD3)- NK cell goal dose >= 1 * 10e7/kg body weight of recipient) as well as the degree of CD3 T-cell contamination (goal CD3+ T-cell dose < 1 * 10e5 / kg body weight of recipient).
- Safety of NK DLI Infusion [ Time Frame: Day +60 after transplant ]The safety evaluation regards transfusion associated adverse events (fever, fall in blood pressure, transfusion site reactions, etc) and is evaluated at the time of NK DLI infusion. The primary long-term safety measure is the absence of acute graft-versus-host disease 30 days after the last NK DLI infusion.
- Efficacy of NK DLI Infusions [ Time Frame: 5 years after last NK DLI ]The efficacy of NK DLI infusions will be assessed by evaluation of the rates of overall and disease free survival and the rate of disease relapse. As this is a single arm study, outcome measures assessed will be compared to those of historical controls treated with haploidentical HSCT without NK DLI infusions.
|Study Start Date:||January 2004|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
|Experimental: NK cell DLI||
Biological: CD3-depleted/CD56+ selected natural killer cells collected from apheresis products
NK DLI products containing >1 10e7 NK cells/kg bodyweight (BW) and < 1 x 10e5 T-cells/kg BW are administered at days +4 (Frankfurt only), and on days +40 and +100 (both centers)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01386619
|Study Chair:||Jakob Passweg, MD||University Hospital, Basel, Switzerland|
|Study Chair:||Dirk Schwabe, MD||Universitätsklinikum Frankfurt|