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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 and over	Pharmaceutical / Industry	AIS-1061-9320 NCI-V95-0689

Objectives

I.  Assess the overall response rate to and safety of CD8+ tumor infiltrating 
lymphocyte (TIL) therapy plus interleukin-2 (IL-2) vs. IL-2 alone in patients 
with metastatic renal cell carcinoma.

II.  Evaluate the 12-month durability of overall response in these patients.

III.  Compare disease stabilization and the time to progression on these two 
regimens.

IV.  Evaluate the relationship between clinical response and TIL phenotype, 
cytokine profile, and cytotoxic activity.

Entry Criteria

Disease Characteristics:

Documented renal cell carcinoma that is metastatic

Primary tumor suitable for radical nephrectomy

Bidimensionally measurable metastases required
  No bone-only disease
  No abdominal metastases requiring surgical clip markers as only site of
     measurable disease

None of the following conditions:
  Solitary kidney
  Nephrotic syndrome
  Refractory symptomatic hypercalcemia (i.e., calcium greater than 12 mg/dl)
  Active CNS metastases (CT or MRI required within 4 weeks prior to entry)
  Clinically significant ascites or pleural effusions

Prior/Concurrent Therapy:

At least 4 weeks since immunosuppressants

Biologic therapy:
  No prior interleukin-2
  At least 4 weeks since any of the following:
     Alpha, beta, and gamma interferons
     Tumor necrosis factor
     Other cytokines (including growth factors and erythropoietin)
     Monoclonal antibodies
     BCG vaccines
     Other biological response modifiers

Chemotherapy:
  At least 4 weeks since chemotherapy

Endocrine therapy:
  At least 4 weeks since megestrol

Radiotherapy:
  No prior irradiation of the kidney
  At least 2 weeks since radiotherapy

Surgery:
  See Disease Characteristics

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0 or 1

Hematopoietic:
  AGC greater than 1,500
  Platelets at least 100,000
  Hb at least 8 g/dl

Hepatic:
  Bilirubin no greater than 1.6 mg/dl (unless due to Gilbert's syndrome)
  SGOT no greater than 4 x ULN
  PTT no greater than 1.5 x control

Renal:
  Creatinine less than 2.0 mg/dl OR
  Creatinine clearance at least 70 ml/min

Cardiovascular:
  No NYHA class III/IV status, e.g.:
     No CHF
     No symptoms of coronary artery disease
     No history of clinically significant arrhythmia
     No poorly controlled hypertension (e.g., diastolic BP > 105 on therapy)
     No prior MI by EKG unless stress test indicates no significant coronary
        artery insufficiency

Pulmonary:
  FEV1 at least 1 liter in patients with clinically significant pulmonary
     disease or history of smoking

Other:
  No active infection
  No active untreated peptic ulcer
  No allergy to gentamicin or streptomycin
  No HIV antibody, HBsAg, or hepatitis C antibody
  No clinically significant CNS disease, e.g.:
     No stroke within 1 year
     No psychiatric disability
     No seizure disorder
  No significant intercurrent illness
  No second malignancy within 5 years except:
     Nonmelanomatous skin cancer
     In situ cervical carcinoma
  No pregnant or nursing women
     Negative pregnancy test within 1 week of entry required of fertile women
  Adequate contraception required of fertile patients

Blood/body fluid analyses and imaging/exams for tumor measurement within 28
days prior to registration

Expected Enrollment

166 evaluable patients will be entered over approximately 1 year.

Outline

Randomized, double-blind study.  Following surgery on Regimen A to obtain 
tumor cells for autologous CD8+ TIL extraction, patients are randomized to 
Arms I and II.  The following acronyms are used:
  IL-2  Interleukin-2 (Chiron), NSC-373364
  PLCB  Placebo
  TIL   Tumor Infiltrating Lymphocytes

Regimen A:  Surgery.  Radical nephrectomy.
Arm I:   Biological Response Modifier Therapy.  IL-2; PLCB.
Arm II:  Biological Response Modifier Therapy.  IL-2; TIL.

Trial Contact Information

Trial Lead Organizations

Applied Immune Sciences, Incorporated

Brent F. Treiger, MD, Protocol chair(Contact information may not be current)		Ph: 408-982-3966