NK DLI in Patients After Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)

Study Overview
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Brief Summary
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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.

Official Title
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Natural Killer Cell Selected T-cell Depleted Donor Lymphocyte Infusions (NK-DLI) in Patients After HLA-haploidentical Allogeneic Stem Cell Transplantation

Conditions
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Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Lymphoma, Neuroblastoma, Rhabdomyosarcoma

Intervention / Treatment
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* Biological: CD3-depleted/CD56+ selected natural killer cells collected from apheresis products


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute/chronic leukemia, myelodysplastic syndrome, lymphoid neoplasia, solid tumor or bone marrow failure syndrome signed informed consent of the patient (or his/her legal representative) Exclusion Criteria: Patients with graft failure Patients with any grade of active acute of chronic graft-versus-host disease (GvHD)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NK cell DLI<br> | Biological: CD3-depleted/CD56+ selected natural killer cells collected from apheresis products<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of NK-DLI production | 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). | At day of transplant (day 0) | 
| Safety of NK DLI Infusion | 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. | Day +60 after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of NK DLI Infusions | 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. | 5 years after last NK DLI |