A Phase I/II study of an in-situ therapeutic cancer vaccine. Vaccines contain a source of antigen and and adjuvant. In this study the source of tumor antigen comes from the killing of a selected tumor by cryoablation (killing using extreme cold) and the adjuvant is intentionally mis-matched immune cells (AlloStim-TM) engineered to produce inflammatory cytokines.
This is a Phase I/II clinical study to investigate the optimal protocol and indication for creating a personalized anti-tumor vaccine within the body of patients with cancer. The aim of the study is to evaluate the safety of administration and anti-tumor effect of a vaccine protocol that has three separate steps. Cancer patients generally present with an immune response to cancer biased to a Th2 response, while a Th1 response is considered necessary for mediating anti-tumor immunity. The first step of the study consists of multiple intradermal priming doses of AlloStimTM. The aim of this step is to create Th1 immunity to the alloantigens in AlloStimTM, thus increasing the number of Th1 cells in circulation. The second step of the protocol involves the cryoablation of a selected tumor lesion followed by an intratumoral AlloStimTM injection. The aim of this step is to generate tumor-specific CTL killer cells in the circulation. The final step is an intravenous infusion of AlloStimTM. The aim of this step is to activate circulating Th1 cells, killer cells, and natural killer cells. The further aim of this step is to create an inflammatory environment that can break-down the ability of the tumor to avoid an anti-tumor immune response. In patients with partial responses and recurrence of disease, additional intravenous "booster" infusions are utilized to reactivate the circulating immune cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Patients meeting eligibility criteria will be primed with at least three and up to nine intradermal AlloStim-TM injections at a frequency of every 2-8 days at doses between 1-4 x 10\^7 cells
Percutaneous cryoablation of selected tumor lesion under CT or US guidance
intratumoral injection of AlloStim-TM into cryoablated tumor lesion at a dose of 1-6 x 10\^7 cells
intravenous AlloStim-TM at doses between 1 x 10\^7 to 1 x 10\^9 cells
Intraperitoneal AlloStim-TM infusion in patients with peritoneal carcinomatosis and/or ascites
Patients with malignant pleural effusion may receive intrapleural AlloStim-TM infusion at a dose of 5-10 x 10\^7 cells.
Patients with palpable tumors may receive alcohol ablation and intratumoral AlloStim-TM
Hadassah-Hebrew University Medical Center
Jerusalem, Israel
The primary endpoint is the evaluation of any drug-related toxicity associated with AlloStimTM administration as well as the reversibility of such toxicity.
Time frame: 90 days
The secondary end-point is the evaluation of the anti-tumor effect of AlloStimTM administration.
Time frame: 1 year
The tertiary end-point is the evaluation of the immunological response to AlloStim-TM administration.
Time frame: 90 days
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