Clinical trial NCT00149006: Cell Therapy of Cancer With Allogeneic Blood Lymphocytes Activated With Recombinant Interleukin-2 (rIL-2) for Metastatic Solid Tumors
Official title: Tumor-Selective and Systemic Cell Therapy of Cancer With Allogeneic Blood Lymphocytes Activated With rIL-2 and Non-Myeloablative Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Tumors
Keywords: Metastatic solid tumor
Mismatch allogeneic cell mediated immunotherapy
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2005-09-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: The present protocol is 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 hematologic malignancies.

Patients with metastatic solid tumors resistant to conventional modalities will be eligible to participate in a treatment program based on the administration of non-myeloablative immunotherapy (i.e. fludarabine, Cytoxan) followed by interferon injections; subsequently the patients will be treated with mismatched alloreactive donor lymphocytes activated in vitro and in vivo with rIL-2. The aim of this study is based on the recognition of foreign tumor cell surface alloantigens.


Eligibility criteria: Inclusion Criteria:

Consenting patients (age \< 70) will be eligible for participation in the study involving selective 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 and sarcomas. Adult patients: Metastatic breast cancer, malignant melanoma, renal cell cancer and selected cases of ovarian cancer, gastrointestinal cancer, small-cell and non-small cell lung cancer with non-bulky metastatic disease, and metastatic prostate cancer.
* Patients with measurable disease evaluable for response with anticipated life expectancy \> 3 months.
* Patients must be \> 2 weeks off of anti-cancer or potentially immunosuppressive treatment.
* Adequate ambulatory performance status (Karnofsky \> 80%; ECOG 0-1) to enable outpatient treatment.
* Compliant and cooperative patients anticipated to be evaluable for response according to the investigator's assessment.
* HLA-compatible (fully matched or single locus mismatched) donor available for allogeneic stem cell transplantation.

Exclusion Criteria:

* Patients with bulky disease or patients with brain metastases resistant to chemo-radiotherapy.
* Patients with a significant history or current evidence of potentially severe cardiovascular or lung disease, or other disease or clinical condition that may not permit accomplishing the planned treatment or drawing conclusions.
* Hepatic and/or renal failure.
* Evidence of serious active infection requiring antibiotic therapy.
* Pregnancy.
* Contraindication for donation due to donor disease: HIV-1; hepatitis B surface antigen (HBsAg) positivity.

Primary outcomes:
measure: Study the feasibility, toxicity, and response rate of allogeneic cell therapy induced by selective intra-lesional and systemic administration of mismatched alloreactive lymphocytes in patients with metastatic cancer
Secondary outcomes:
measure: Study the feasibility, toxicity, and response to treatment with allogeneic mini-transplant using sibling donors in patients with metastatic cancer
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
Study officials:
affiliation: Hadassah Medical Organization
name: Shimon Slavin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hadassah Medical Organization
name: Reuven Or, MD
role: STUDY_DIRECTOR
References: