Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CCF-RPC-3209R NCI-T92-0172O, T92-0172

Objectives

I.  Continue a Phase II trial of tumor infiltrating lymphocytes (TIL) 
administered with continuous-infusion interleukin-2 (IL-2) in patients with 
metastatic renal cell carcinoma, following TIL expansion in vitro with IL-2 
and interleukin-4 (IL-4) and restimulation with autologous tumor cells.

II.  Characterize the phenotypes and cytolytic potency of the effector cell 
population in the expanded TIL.

III.  Characterize the phenotype and lytic activity of lymphocytes in 
metastatic lesions of treated patients.

IV.  Determine, using indium-111 labeling, the in vivo distribution of TIL 
expanded in vitro with IL-4/IL-2.

Entry Criteria

Disease Characteristics:

Histologically confirmed, surgically incurable, metastatic
renal cell carcinoma
  Nephrectomy or removal of metastatic lesion required for TIL
  preparation

Objectively measurable disease required

Minimal tumor burden, defined as all of the following,
required:
  Post nephrectomy status (patients with unresected primary who
  are otherwise eligible undergo nephrectomy prior to entry)

  No more than 30% of the liver metastatically involved (as
  determined by CT scan)

  Calcium no higher than 11.0 mg/dl in the presence of osseous
  metastases

  No CNS metastases, confirmed by normal CT scan of the head

  (No restrictions apply to pulmonary metastases)

No significant effusions or ascites

Prior/Concurrent Therapy:

Biologic therapy:
  No more than 1 prior immunotherapy regimen

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  No concurrent corticosteroids

Radiotherapy:
  Prior radiotherapy for palliation of painful skeletal
     metastases allowed
  At least 4 weeks since prior radiotherapy

Surgery:
  Nephrectomy to remove primary tumor required prior to entry
  At least 14 days since prior surgery

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0 or 1

Life expectancy:
  At least 3 months

Hematopoietic:
  WBC at least 4,000
  Platelets at least 100,000
  Hb at least 10.0 g/dl

Hepatic:
  Bilirubin no more than 1.5 mg/dl

Renal:
  Creatinine no more than 1.8 mg/dl and/or
  Creatinine clearance at least 60 ml/min

Cardiovascular:
  LVEF at least 50%
  No NYHA class III/IV disease
  No history of CHF
  No MI
  No angina
  No serious arrhythmia
  No contraindication to the use of pressor agents

Pulmonary:
  DLCO at least 50%

Other:
  No active infection requiring antibiotics within 3 weeks of
     entry
  No history of malignant hyperthermia
  Negative HTLV-III ELISA antibody test
  No HBsAg
  No history of a second malignancy within 5 years except:
     Carcinoma in situ of the cervix
     Basal cell carcinoma of the skin
  Negative pregnancy test required of fertile women
  Contraception use required of fertile women

Expected Enrollment

A total of 25 patients will be accrued over 12 months.  If no response is seen 
in the first 14 patients, accrual will cease.

Outline

Nonrandomized study.  Eligible patients with unresected primaries will undergo 
nephrectomy prior to protocol treatment.

Biological Response Modifier Therapy.  Tumor Infiltrating Lymphocytes, TIL, 
expanded in vitro with Interleukin-2, (Hoffmann-La Roche), IL-2, NSC-600664 
and Interleukin-4 (Schering-Plough), IL-4, NSC-618085, and restimulated with 
autologous tumor cells; systemic IL-2.

Olencki T, Finke J, Lorenzi V, et al.: Adoptive immunotherapy (AIT) for renal cell carcinoma (RCC) tumor infiltrating lymphocytes (TIL's) cultured in vitro with rIL-2, rhIL-4, and autologous tumor: a phase II trial. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-762, 244, 1994.

Trial Contact Information

Trial Lead Organizations

Cleveland Clinic Foundation Hospital

Ronald Bukowski, MD, Protocol chair		Ph: 216-444-6825; 800-862-7798