20 patients with invasive castration resistant prostate cancer and radiologically verified metastases will be enrolled into the Phase I Clinical Trial. The trial is a dendritic cell based immunotherapy. Autologous dendritic cells will be obtained by leukapheresis and elutriation and stimulation by cytokines. The induced dendritic cells will have to pass viability, immunophenotyping and sterility criteria and will be injected into a cryoablated region of the primary prostate cancer tumor. The treatment is supplemented by immunomodulatory regimens.
The study treatment dendritic cells (ACT2001) will be injected into the prostate following prostatic cryoablation. It is speculated that antigen from the cryoablated cancer will be available in the vicinity of the cryoablation field immediately following the procedure. Autologous, immature dendritic cells are capable of internalizing antigen, migrating to the lymphatic system, and presenting antigenic epitopes to T lymphocytes. In this way, dendritic cells are capable of initiating a cell-mediated systemic immune response. In concept, the cancer itself should provide a specific and potentially broad spectrum of cancer-related antigens. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted using a regimen of low-dose cyclophosphamide. Low-dose cyclophosphamide has been empirically shown to selectively deplete the number of circulating regulatory T cells. The second half of patients will in addition receive treatment with the the immune checkpoint inhibitor ipilimumab antibody as one additional measure to avoid cancer cell immune evasion. Using this combination of therapies, it is thought that a clinically significant anti-cancer immune response might be elicited.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Autologous dendritic cells will be obtained following leukapheresis and cytokine induction and will be injected into cryoablated prostate cancer tissue under ultrasound guidance.
Low-dose cyclophosphamide will be given metronomically for the purpose of selective inhibition of T regulatory cells for 6 months following start of treatment.
The antibody and immune checkpoint inhibitor ipilimumab (Yervoy) will be given for the last 10 patients enrolled into the study in addition to cryoimmunotherapy and low-dose cyclophosphamide.
Haukeland University Hospital Research Department
Bergen, Hordaland, Norway
Composite measure of the safety and toxicity profile, including definition of the Maximum Tolerated Dose.
Maximum dose dendritic cells administered was well tolerated by interim analysis of 13 patients with database lock September 15th 2017
Time frame: 72 weeks
Pembrolizumab tested to boost dendritic cell-based immunity of patients 16 to 18 (3 last recruited patients to the trial).
200 mg pembrolizumab i.v. post-CryoIT was well tolerated - effect is under evaluation.
Time frame: 52 weeks
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