This is a phase I study which will test the safety of different doses of the patients own immune cells which have been changed to help recognize and destroy the cancer cells. The investigators want to find out what effects, good and/or bad, it has on the body and on the prostate cancer. The immune cells (T cells) used in this study will be the patients own immune cells. They will be removed from the patients blood, changed in the laboratory, and then put back into their body. T cells help the body fight infections. These cells may also kill cancer cells in some cases. Right now the patients T cells are unable to kill the cancer cells. For this reason, the physician will change the T cells by putting in a gene so that they may be able to better recognize and kill the prostate cancer cells. A gene is a portion of information which comes from the DNA and tells the cell what to do. This gene will be put into the patients T cells by a weakened virus. It is hoped that this approach will help the T cells recognize the prostate cancer tumor cells and possibly kill them. The investigators have found that T cells modified in this way were able to cure a cancer similar to Chronic Lymphocytic Leukemia in mice. However, this is an entirely new treatment for prostate cancer and it is not known if it will have any beneficial or unexpected harmful effects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Three cohorts of patients each will receive escalating doses of transduced autologous chimeric T lymphocytes at 1 x 10\^7 CAR+ T cells/kg, 3 x 10\^7 CAR+ T cells/kg, and 1 x 108 CAR+ T cells/kg, respectively. One patient will be initially added to the three already enrolled in cohort 1 using a new variant vector expressing the P28z CAR, and up to three patients may be added to each cohort, for a total of up to six each, in the case of Grade 3 toxicity and/or sub-optimal imaging. A 4th cohort of three patients may be added if an anti-PSMA effect is observed either immunologically or radiographically or if there is preferential targeting of the cells at a particular dose level. The dose level of the 4th cohort would be from a previously tested dose level. All patients will receive one dose of cyclophosphamide (Cy) at 300mg/m2 iv one day prior to infusion of T cells.
Three cohorts of patients each will receive escalating doses of transduced autologous chimeric T lymphocytes at 1 x 10\^7 CAR+ T cells/kg, 3 x 10\^7 CAR+ T cells/kg, and 1 x 10\^8 CAR+ T cells/kg, respectively. One patient will be initially added to the three already enrolled in cohort 1 using a new variant vector expressing the P28z CAR, and up to three patients may be added to each cohort, for a total of up to six each, in the case of Grade 3 toxicity and/or sub-optimal imaging. A 4th cohort of three patients may be added if an anti-PSMA effect is observed either immunologically or radiographically or if there is preferential targeting of the cells at a particular dose level. The dose level of the 4th cohort would be from a previously tested dose level. All patients will receive one dose of cyclophosphamide (Cy) at 300mg/m2 iv one day prior to infusion of T cells.
Memorial Sloan Kettering Cancer Center
New York, New York, United States
The safety and tolerability of immunotherapy
Dose escalation is based on the dose limiting toxicity (DLT). In this phase I trial, dose escalation will be based on the DLT, defined as a grade 3 or 4 toxicity (excluding alopecia, fatigue) developing after infusion of the T cells as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Scale (CTCAE) Version 3.0. Only toxicities that are possibly, probably, or definitely related to treatment will be considered DLTs. Patients will be observed for DLTs four weeks (28 days) from the T cell infusion
Time frame: 4 weeks
Changes in bone metastases
Time frame: Week 12 then every 3 months
Changes in biomarkers of bone metastasis and metabolism
Time frame: Week 4 and week 12
Changes in circulating tumor cells
Time frame: Weeks 4, 12, 24 and every 3 months
Humoral and cell-mediated immunity to PSMA and other known prostate cancer antigens
Time frame: Weeks 12 and 24
To assess patterns of change in PSA.
Time frame: 5 years
To track the persistence, accumulation, and migration of genetically retargeted anti-PSMA autologous T cells
Time frame: 2 years
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