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The purpose of this study is to find out how many irradiated natural killer (NK) cells can be safely given to patients with cancer that has recurred after an autologous stem cell transplant, and to see what effects (good and bad) it has on the patient and their cancer. This research is being done because currently, there is no cure or effective treatment for blood-borne cancers when it has come back after an autologous stem cell transplant.
Patients with hematological malignancies such as acute leukemia, lymphoma, Hodgkin's disease and myeloma, are generally treated initially with chemotherapy, radiotherapy or a combination of both. High dose therapy and autotransplantation are often utilized in the management of such patients, either as part of initial therapy or for treatment of relapsed disease. When a patient's cancer relapses after transplantation, the prognosis is dismal. Therapeutic options are usually limited to palliative chemotherapy and/or local radiation, and for persons with excellent performance status experimental treatments are considered on an ad hoc basis.
Much interest in the last decade has focused on the role of cellular and immunotherapy in this setting. Cancer vaccines and the administration of adoptive cellular and immunotherapy have the theoretical advantage of being non cross-reactive with previous treatments (such as radiotherapy and chemotherapy) and are currently under investigation using a variety of methodologies. NK cells comprise roughly 15% of all lymphocytes in the peripheral blood. They normally function as part of the innate immune system, which provides the body's initial response to infection and malignancy. However, patients with malignancies frequently have impaired NK cell function, as evidenced by reduced in vitro proliferative responses and reduced cytotoxic activity. The infusion of an irradiated NK cell line is appealing as it is a source of cells that can be expanded to therapeutic quantities, and retains anti-tumor activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NK-92 cells | Experimental | Preparation of irradiated NK-92 cells suspended in a saline and plasma solution. NK-92 working cell bank was established from a master cell bank supplied by Conkwest Inc. (San Diego CA). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NK-92 cells | Biological | Cells are administered as an intravenous infusion over one hour on days 1, 3 and 5 of each cycle of treatment. Patients can receive up to 6 cycles, which are administered monthly. Cell dosage is as follows:
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine if there are any dose limiting toxicities to this therapy, as well as the maximum tolerated dose. | Day 1, 3, and 5 of each cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Document any preliminary efficacy information from the NK-92 cell infusion. | 6 months | |
| Assess any immune response directed against the infused NK-92 cells. | 28 days after each cycle | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Armand Keating, MD | Princess Margaret Hospital, Canada | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14985163 | Background | Klingemann HG, Martinson J. Ex vivo expansion of natural killer cells for clinical applications. Cytotherapy. 2004;6(1):15-22. doi: 10.1080/14653240310004548. | |
| 8152260 | Background | Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994 Apr;8(4):652-8. |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D054219 | Neoplasms, Plasma Cell |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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|
| Determine kinetics of infused NK92 cells. |
| Pre-infusion, 15 min, 2h, 6h, 24h, 48h, 168h post infusion |
| 10417052 | Background | Tam YK, Miyagawa B, Ho VC, Klingemann HG. Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J Hematother. 1999 Jun;8(3):281-90. doi: 10.1089/106161299320316. |
| 12796791 | Background | Maki G, Tam YK, Berkahn L, Klingemann HG. Ex vivo purging with NK-92 prior to autografting for chronic myelogenous leukemia. Bone Marrow Transplant. 2003 Jun;31(12):1119-25. doi: 10.1038/sj.bmt.1704117. |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |