RATIONALE: Biological therapies use different ways to stimulate the immune system and stop
tumor cells from growing. Treating a person's T cells in the laboratory and then reinfusing
them may cause a stronger immune response and kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of T-cell therapy in treating patients who
have prostate cancer that has not responded to hormone therapy.
- Determine the safety of activated autologous T cells (Xcellerate) therapy in patients
with hormone-refractory prostate cancer.
- Determine the change in prostate-specific antigen (PSA) levels in patients treated with
- Determine the effects on bone in patients treated with this therapy.
OUTLINE: This is a multicenter study.
Patients undergo leukapheresis to collect peripheral blood mononuclear cells (PBMC). PBMC
are activated and expanded ex vivo by costimulation with antihuman CD3 and antihuman CD28
monoclonal antibodies covalently attached to superparamagnetic microbeads (Xcellerate).
Xcellerate-activated T cells are reinfused on day 0.
Patients are followed weekly for 4 weeks and then monthly for 3 months.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
- Histologically confirmed adenocarcinoma of the prostate
- Evidence of androgen-independent disease
- Patient must have received prior primary hormonal therapy (e.g.,
orchiectomy or gonadotropin-releasing hormone analog with or without
- Demonstrated disease progression by any 1 of the following:
- Elevated PSA level (at least 5 ng/mL) that has serially risen from
baseline on 2 occasions at least 1 week apart
- At least 1 new osseous lesion on bone scan
- More than 25% increase in the sum of the products of the perpendicular
diameters of all bidimensionally measurable sites of disease
- No CNS metastases
- Not specified
- ECOG 0-1
- At least 3 months
- Not specified
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- SGPT no greater than 1.5 times ULN
- Hepatitis B surface antigen negative
- No active or chronic hepatitis B or C
- No other hepatic dysfunction that would preclude study
- Creatinine less than 2.0 mg/dL
- Calcium less than 11 mg/dL
- No renal dysfunction that would preclude study
- No symptomatic hypercalcemia
- No New York Heart Association class III or IV heart disease
- No pulmonary disease requiring inhaled steroids or bronchodilators
- No history of HIV 1 or 2 or human T-cell lymphotrophic virus (HTLV) 1 or 2
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer
- No history of autoimmune disease (e.g., rheumatoid arthritis or multiple sclerosis)
- No other major organ system dysfunction
- No gastrointestinal, neurologic, or psychiatric dysfunction that would preclude study
- Human anti-mouse antibody negative
PRIOR CONCURRENT THERAPY:
- No concurrent growth factors, interleukin, interferons, or cytokines
- No prior chemotherapy or other systemic chemotherapy agent for prostate or any other
- Prior aminoglutethimide allowed
- At least 4 weeks since prior flutamide
- At least 6 weeks since prior bicalutamide or nilutamide
- Concurrent luteinizing hormone-releasing hormone agonists should be continued
- No concurrent corticosteroids or dexamethasone
- No concurrent anti-androgens (e.g., flutamide, bicalutamide, or nilutamide)
- At least 4 weeks since prior local radiotherapy
- No prior radiopharmaceutical therapy (e.g., strontium chloride Sr 89 or samarium Sm
153 lexidronam pentasodium)
- No concurrent radiotherapy
- Not specified
- Prior ketoconazole or PC-SPES allowed
- At least 1 week since prior antibiotic, antifungal, or antiviral agents
- At least 4 weeks since other prior systemic therapy for prostate cancer (except
bisphosphonates or hormonal therapy)
- At least 6 weeks since prior investigational drugs or devices
- No other concurrent therapy for this disease
- No concurrent participation in another clinical trial
- No concurrent bisphosphonates unless initiated prior to study
- No concurrent immunosuppressive drugs
- No other concurrent experimental therapies