This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Approximately 30 subjects will be enrolled in this study at UPMC/UPCI Hillman Cancer Center. The study participants in this trial will be HLA-A2 positive male or female adults over 18 years of age. The primary objective is to establish the safety of this approach. The endpoints will be to determine the maximum tolerated dose (MTD) of alpha-DC1 vaccines in combination with a fixed dose of poly-ICLC, using standard criteria and close clinical followups. The secondary objectives are 1) to assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays; and 2) to assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and 4- and 6-month progression-free survival (PFS).
This is a single-institution Phase I/II study designed to evaluate the safety, the induction of an immune response, and the preliminary clinical response of vaccinations with Type-1 αDCs (αDC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. The hypothesis is that this form of vaccines in combination with poly-ICLC treatment will prove to be safe, and will induce potent anti-glioma immune responses. The primary objective is to establish the safety of the approach. The secondary objectives are to 1) assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays and 2) assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and four- and six-month progression-free survival (PFS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Subjects will receive four (4) injections of the vaccine into the lymph nodes. Injection is guided by ultrasonography. Subjects will receive the first cycle of vaccine in the right groin. Two weeks after the first vaccine, subjects receive the same vaccine at the left groin, followed by the 3rd and the 4th vaccines in the left and right armpits, respectively, with two-week intervals. Each injection contains 0.2cc (less than 1/20th of a teaspoon) of a saline solution containing the vaccine cell mixture.
This phase will begin at week 13. These subjects will be treated with additional vaccinations every 4 weeks to a maximum of 5 vaccine injections and, if poly-ICLC is available from the supplier starting on the day of the first additional vaccine and twice/week for 8 injections following each additional vaccine. If poly-ICLC supply is not available from the supplier, DC vaccines only will be given in the booster phases.
At week 33, following the completion of 5 additional vaccines, if participants demonstrate stable disease or positive clinical response, if poly-ICLC supply is still available, participants will be offered additional DC-vaccines and poly-ICLC treatment. The second phase booster vaccines can be continued as long as the patient shows continued positive response or stable disease (both radiological and clinically) with no major adverse events, and as long as funding is available for the study. DC vaccines in this phase will be administered every 6 months+/- 2 weeks. 2). Poly-ICLC at 10µg/kg and up to 1640 µg/injection will be administered intramuscularly (i.m.) on the day of each booster DC vaccine. Poly-ICLC will be administered weekly thereafter for twice (at one week and two weeks after each vaccine) (e.g. if the previous DC vaccine was administered on a Thursday, subsequent poly-ICLC will be administered on the next two Thursdays
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Number of Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT)
Number of participants who experienced treatment-related Dose Limiting Toxicities (DLT) at any dose level.
Time frame: up to 8 weeks
Median Time To Progression
Median number of months until disease progression. Tumor size was assessed using magnetic resonance imaging (MRI) scans with contrast enhancement to detect change from baseline.
Time frame: At baseline, 9, 17, 25, and 33 weeks, and every 3 months; up to 23 months
12-month- Progression Free Survival (PFS)
Number of patients with progression-free status lasting at least 12 months
Time frame: Up to 12 months
Overall Survival (OS)
Time interval from start of treatment until date of death.
Time frame: Up to 102 months
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