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The present protocol is a phase 2 study designed to investigate the potential application of allogeneic cell-mediated immunotherapy in metastatic solid tumors, similarly to the well established graft versus leukemia (GVL) effects, in patients with metastatic solid tumors resistant to conventional treatment modalities. Patients will be eligible to participate in a treatment program based on systemic administration of mismatched lymphocytes activated in vitro with rIL-2 (LAK) followed by rIL-2 inoculation in vivo. This treatment is aiming to induce an anti-tumor effect mediated by the efficient killing activity of the rIL-2 activated cells. Prior to cell infusion patients will receive the conditioning treatment with low dose Cyclophosphamide (Cyc) or Fludarabine with 2 injections of low dose alpha interferon. Cell therapy will be combined with specific anti-tumor monoclonal antibodies if available for the specific disease. Further activation of the anti-tumor activity of alloreactive donor T cells and natural killer (NK) cells will be accomplished by in vivo inoculation of rIL-2, aiming for enhancing the anti-cancer potential of donor-derived effectors cells. Patients will receive one - three cycles of cell therapy, as long as there are no signs of Graft- versus - Host - disease (GVHD) and the malignant disease is controlled.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| one - three cycles of cell therapy during 4-6 weeks (3-5x10^7 cells/kg will be given through IV systemically | Procedure | Patients will be eligible to participate in a treatment program based on systemic administration of mismatched lymphocytes activated in vitro with rIL-2(LAK) followed by rIL-2 inoculation in vivo |
| Measure | Description | Time Frame |
|---|---|---|
| CR:disappearance of disease.PR:<50% decrease in the total tumor load of the lesions SD:<50% reduction and 25% increase in the sum of the products of the longest perpendicular diameters of the measured lesions.PD:>25% increase in the size of lesion. | on day +7 day +17, day +28 post cell therapy. |
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Inclusion Criteria:
Consenting patients (age 12-70) will be eligible for participation in the study involving anti-tumor immunotherapy provided the following criteria are met:
Evidence of cancer not expected to be cured with conventional modalities:
Pediatric patients: Chemotherapy-resistant neuroblastoma stage 4 & sarcomas. Adult patients: Metastatic breast cancer, malignant melanoma, renal cell cancer and selected cases of ovary cancer, gastrointestinal cancer, small-cell and non-small cell lung cancer with non-bulky metastatic disease, metastatic prostate cancer.
Patients with measurable disease evaluable for response with anticipated life expectancy >3 months.
Patients must be >2 weeks off anti-cancer or potentially immunosuppressive treatment.
Adequate ambulatory performance status (Karnofsky >80%; ECOG 0-1) to enable outpatient treatment (see Appendix 1).
Compliant and cooperative patients anticipated to be evaluable for response according to investigator's assessment.
HLA-noncompatible (partial matched or mismatched) donor available.
Exclusion Criteria:
Patients will be excluded from participation in the study if any of the following criteria are met:
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| Name | Affiliation | Role |
|---|---|---|
| Reuven Or, Prof., M.D. | Hadassah University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hadassah University Hospital | Jerusalem | 91120 | Israel |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D008545 | Melanoma |
| D002292 | Carcinoma, Renal Cell |
| D005770 | Gastrointestinal Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
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