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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NK cell DLI | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD3-depleted/CD56+ selected natural killer cells collected from apheresis products | Biological | 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) |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jakob Passweg, MD | University Hospital, Basel, Switzerland | Study Chair |
| Dirk Schwabe, MD | Johann Wolfgang Goethe University Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum | Frankfurt | Germany | ||||
| University Hospital |
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| Basel |
| Switzerland |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D009190 | Myelodysplastic Syndromes |
| D008223 | Lymphoma |
| D009447 | Neuroblastoma |
| D012208 | Rhabdomyosarcoma |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001855 | Bone Marrow Diseases |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D009217 | Myosarcoma |
| D009379 | Neoplasms, Muscle Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D012509 | Sarcoma |
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