RATIONALE: Biological therapies use different ways to stimulate the immune system and stop
cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells
from dividing so they stop growing or die. Combining biological therapy with chemotherapy
may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of biological therapy combined with
chemotherapy in treating patients who have metastatic kidney cancer or colorectal cancer.
- 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
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
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.
- 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
- No untreated or unstable, treated brain metastasis
- 18 and over
- ECOG 0-2
- More than 3 months
- 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
- 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
- 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
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No thrombophlebitis
- FEV_1 and FVC at least 65% predicted
- No uncontrolled pulmonary embolism
- 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
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- At least 4 weeks since prior steroid therapy or steroid-containing compounds
- At least 2 weeks since prior topical or inhaled steroids
- More than 4 weeks since prior radiotherapy and recovered
- More than 4 weeks since prior major surgery
- No other concurrent investigational agents
- No other concurrent commercial anticancer agents
- No concurrent combination antiretroviral therapy for HIV-positive patients