Clinical trial NCT00855452: Activated Allogeneic Lymphocytes for Induction Graft Versus Tumor Effect in Metastatic Solid Tumors
Official title: rIL-2 Activated Allogeneic Lymphocytes for the Induction of Graft Versus Tumor Effect (GVT) in Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Malignant Melanoma
Renal Cell Cancer
Gastrointestinal Cancer
Keywords: GVL
rIL-2(LAK)
GVHD
MST
alloCT
alloBMT
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2009-03-04
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

1. 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.
2. Patients with measurable disease evaluable for response with anticipated life expectancy \>3 months.
3. Patients must be \>2 weeks off anti-cancer or potentially immunosuppressive treatment.
4. Adequate ambulatory performance status (Karnofsky \>80%; ECOG 0-1) to enable outpatient treatment (see Appendix 1).
5. Compliant and cooperative patients anticipated to be evaluable for response according to investigator's assessment.
6. 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:

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

Primary outcomes:
measure: 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.
timeFrame: on day +7 day +17, day +28 post cell therapy.
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
Study officials:
affiliation: Hadassah University Hospital
name: Reuven Or, Prof., M.D.
role: PRINCIPAL_INVESTIGATOR
References: