• Response as measured by RECIST guidelines and Kaplan-Meier method at 5 years [ Designated as safety issue: No ]
  
• Survival as measured by the Kaplan-Meier method at 5 years [ Designated as safety issue: No ]
  
• Safety as measured by NCI common toxicity table at study completion [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Determine the safety of a repeat course of interleukin-12-primed activated T cells (12ATC) in combination with fluorouracil, sargramostim (GM-CSF), and interferon alfa-2b in patients with metastatic renal cell or colorectal carcinoma.
• Determine the clinical responses of patients treated with this regimen.
• Determine the efficacy of 12ATC in these patients.
• Determine whether there are changes in immunologic parameters related to 12ATC as measured by lymphocyte phenotype and cytokine secretion in these patients.
• Determine the correlation between clinical responses in patients treated with this regimen and in vitro immune functions of lymphocytes.

OUTLINE: Patients are stratified according to disease type (renal cell carcinoma vs colorectal carcinoma).

Patients receive sargramostim (GM-CSF) subcutaneously (SC) daily on days 1-5 and then undergo collection of autologous peripheral blood mononuclear cells (PBMC) on days 6 and 7 of week 1. The PBMC are treated ex vivo to form interleukin-12-primed activated T cells (12ATC).

Patients receive fluorouracil IV over 24 hours on day 6 of week 2 and interferon alfa-2b SC and GM-CSF SC 3 times weekly on weeks 3-5. Patients receive 12ATC IV over 15-30 minutes twice weekly and interferon alfa-2b SC (at least 24 hours after 12ATC infusion) once weekly on weeks 6-8. Patients with complete or partial response or stable disease at 3 weeks after the last 12ATC infusion may receive an additional 8-week course as above.

Patients are followed every 2-3 months for 1 year and then every 6 months for 2 years or at any time when the physical examination or symptoms are suspicious for tumor progression.

PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 2-3 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic renal cell carcinoma or colorectal carcinoma, meeting 1 of the following criteria:

  • Obtained no benefit from prior standard or salvage therapy
  • Ineligible for standard therapy because of concurrent illness
  • Declined standard therapy

• At least 1 site of measurable disease that can be measured in at least 1 dimension

  • At least 20 mm with conventional techniques OR at least 10 mm with spiral CT scan
• No untreated or unstable, treated brain metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 4,000/mm^3
• Granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• No coagulation disorders

Hepatic:

• Bilirubin no greater than 2.5 mg/dL*
• ALT/AST less than 3 times upper limit of normal*
• PT no greater than 1.5 times control (unless therapeutically anticoagulated)
• PTT less than 1.5 times control (unless therapeutically anticoagulated) NOTE: *Patients whose cancer has led to values that do not fall within the above ranges may be eligible at the discretion of the investigators

Renal:

• Creatinine no greater than 2.0 mg/dL* NOTE: *Patients whose cancer has led to values that do not fall within the above range may be eligible at the discretion of the investigators

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No thrombophlebitis

Pulmonary:

• FEV_1 and FVC at least 65% predicted
• No uncontrolled pulmonary embolism

Other:

• No other malignancy within the past 5 years except resected basal cell skin cancer or carcinoma in situ of the cervix
• No prior allergic reactions attributed to compounds of similar chemical or biologic composition to interleukin-12-primed activated T cells or other study agents
• No active autoimmune disease
• No uncontrolled thyroid abnormalities
• No ongoing or active infection
• No other uncontrolled concurrent illness
• No psychiatric illness or social situations that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 2 years after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• More than 4 weeks since prior immunotherapy

Chemotherapy:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• At least 4 weeks since prior steroid therapy or steroid-containing compounds
• At least 2 weeks since prior topical or inhaled steroids

Radiotherapy:

• More than 4 weeks since prior radiotherapy and recovered

Surgery:

• More than 4 weeks since prior major surgery

Other:

• No other concurrent investigational agents
• No other concurrent commercial anticancer agents
• No concurrent combination antiretroviral therapy for HIV-positive patients