This was a single-center, randomized, open-label multi-arm phase II clinical trial. The study protocol was approved by an independent ethics committee, institutional review board and internal scientific peer review committee at the University of California, Los Angeles. Patients were recruited and completed treatment between 2010 and 2014, with survival follow-up until the present date. Subjects were not compensated, and all patients gave written informed consent before enrollment.
Twenty-three patients with high-grade WHO Grade III or IV gliomas were enrolled in this protocol. To be eligible for the primary cohort, patients had to be >18 years and have newly diagnosed or recurrent WHO Grade III or IV malignant glioma, as determined through central pathology review. For all patients, a Karnofsky Performance Score (KPS) of ≥60, adequate bone marrow, liver, and renal function, life expectancy of ≥8 weeks, no other prior malignancy within the last 5 years, no active viral infections, and sufficient resected tumor material to produce the autologous vaccine were required. All newly diagnosed patients underwent surgical resection followed by radiation and chemotherapy with temozolomide for 6 weeks, per standard of care. Patients in the recurrent setting proceeded to trial treatment after recovery from surgery. All patients were scheduled to receive ATL-DC. Patients were then randomized to receive either placebo, resiquimod (topical 0.2%, 3 M), or poly-ICLC (20 μg/kg i.m., Oncovir) as an adjuvant to the DC vaccine. Patients underwent leukapheresis to obtain adequate numbers of PBMC for DC generation. For the study treatment, we processed the resected tumor tissue into a lysate, then prepared and cryopreserved the autologous DCs as we previously described2 (link),3 (link). Patients were then treated with three intradermal injections of autologous tumor lysate-pulsed DC plus adjuvant TLRs/placebo on days 0, 14, and 28. The TLR agonists were delivered as separate injections. Poly ICLC (20 ug/kg) was given as an intramuscular injection at the same site as the intradermal ATL-DC vaccine. Resiquimod (0.2%) was applied as a topical gel directly over the intradermal ATL-DC vaccine site. The placebo was a gel without any resiquimod and administered similarly over the intradermal vaccine site. All vaccines were administered on the upper arm. Follow-up for patients was conducted at the study site for vital signs, KPS, hematology and serum chemistries, as well as neurological and physical examinations.
Twenty-three patients with high-grade WHO Grade III or IV gliomas were enrolled in this protocol. To be eligible for the primary cohort, patients had to be >18 years and have newly diagnosed or recurrent WHO Grade III or IV malignant glioma, as determined through central pathology review. For all patients, a Karnofsky Performance Score (KPS) of ≥60, adequate bone marrow, liver, and renal function, life expectancy of ≥8 weeks, no other prior malignancy within the last 5 years, no active viral infections, and sufficient resected tumor material to produce the autologous vaccine were required. All newly diagnosed patients underwent surgical resection followed by radiation and chemotherapy with temozolomide for 6 weeks, per standard of care. Patients in the recurrent setting proceeded to trial treatment after recovery from surgery. All patients were scheduled to receive ATL-DC. Patients were then randomized to receive either placebo, resiquimod (topical 0.2%, 3 M), or poly-ICLC (20 μg/kg i.m., Oncovir) as an adjuvant to the DC vaccine. Patients underwent leukapheresis to obtain adequate numbers of PBMC for DC generation. For the study treatment, we processed the resected tumor tissue into a lysate, then prepared and cryopreserved the autologous DCs as we previously described2 (link),3 (link). Patients were then treated with three intradermal injections of autologous tumor lysate-pulsed DC plus adjuvant TLRs/placebo on days 0, 14, and 28. The TLR agonists were delivered as separate injections. Poly ICLC (20 ug/kg) was given as an intramuscular injection at the same site as the intradermal ATL-DC vaccine. Resiquimod (0.2%) was applied as a topical gel directly over the intradermal ATL-DC vaccine site. The placebo was a gel without any resiquimod and administered similarly over the intradermal vaccine site. All vaccines were administered on the upper arm. Follow-up for patients was conducted at the study site for vital signs, KPS, hematology and serum chemistries, as well as neurological and physical examinations.
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