Activated Allogeneic Lymphocytes for Induction Graft Versus Tumor Effect in Metastatic Solid Tumors

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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Key information

Conditions

Metastatic Breast Cancer Adenocarcinoma Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Renal Cell Digestive System Diseases Digestive System Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Malignant Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Renal Cell Cancer Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

12 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hadassah University Hospital

Jerusalem, 91120, Israel

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:

Any of the above criteria are not met.
Patients with a significant history or current evidence of potentially severe cardiovascular disease.
Hepatic and/or renal failure.
Abnormal PT and PTT.
Patients with abnormal hemogram (PMN<1.0x109/L; HB<10; Plts<50x109/L)
Evidence of serious active infection requiring antibiotic therapy.
Evidence of active disease requiring steroid or cytotoxic therapy.
Pregnancy.
Contraindication for donation due to donor disease: HIV-1; HBsAg positivity.

Treatment and study plan

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

Primary outcomes

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.

Time frame: on day +7 day +17, day +28 post cell therapy.

Sponsors and collaborators

Lead sponsor

Hadassah Medical Organization

Other

Registry information

Official study title

rIL-2 Activated Allogeneic Lymphocytes for the Induction of Graft Versus Tumor Effect (GVT) in Metastatic Solid Tumors

Acronym: rIL-2(LAK)

Important dates

Study start: 2009
Primary completion: 2014
Study completion: 2014
First posted: Mar 4, 2009
Registry last updated: Jun 11, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed