020221

This Phase III trial is designed to evaluate the impact on survival time, as well as safety, in patients following treatment with DCVax(R)-L, an immunotherapy treatment for GBM. The experimental therapy uses a patient's own tumor lysate and white blood cells from which precursors of the dendritic cells are isolated. The dendritic cell is the starter engine of the immune system. The white cells are then made into dendritic cells and they are educated to "teach" the immune system how to recognize brain cancer cells. Eligible patients will receive a series of injections of DCVax-L, to activate and then boost the immune response to the tumor cells.

The primary study endpoint is OS (overall survival) compared to external controls in newly diagnosed glioblastoma, and the first secondary endpoint is OS compared to external controls in recurrent glioblastoma.

Side effects reported from early trials are mostly mild, and may include skin reactions of redness, pain \& swelling at the injection site.

Inclusion Criteria:

All patients must meet the following inclusion criteria. All tests and eligibility criteria must be completed within four weeks of completion of radiation and chemotherapy, following surgery.

* Patients must have sufficient tumor lysate protein that was generated from the surgically obtained tumor material. Patients must also have sufficient DCVax-L product available after manufacturing. These determinations will be made by Cognate BioServices, Inc. (Cognate) and communicated to the clinical site through the Sponsor, or its designee.
* Patients with newly diagnosed, unilateral GBM (Grade IV) are eligible for this protocol. An independent neuropathologist will review this diagnosis during the enrollment process.
* Subjects ≥18 and ≤70 years of age at surgery who are capable of informed consent. Patients must be able to understand and sign the informed consent documents indicating that they are aware of the investigational nature of this study.
* Patients must have a life expectancy of \>8 weeks.
* Patients must have a KPS rating of ≥70 at the baseline visit (Visit 3).
* Primary therapy must consist of surgical resection with the intent for a gross or near total resection of the contrast-enhancing tumor mass, followed by conventional external beam radiation therapy and concurrent Temodar chemotherapy. Patients having a biopsy only will be excluded. These primary treatments must be completed at least two weeks prior to first immunization.
* Patients may have received steroid therapy as part of their primary treatment. Steroid treatment must be stopped at least 10 days prior to leukapheresis.
* Patients must not have progressive disease at completion of radiation therapy. Patients with suspected pseudoprogression will be enrolled and analyzed separately.
* Patients must be willing to forego cytotoxic anti-tumor therapies except temozolomide essentially according to the schedule of the Stupp Protocol (Stupp et al. N Engl J Med 352: 987-96, 2005) while being treated with DCVax-L. DCVax-L treatment must be given as described and temozolomide/Temodar treatment schedules must be given essentially according to the Stupp Protocol.
* Patients must have adequate bone marrow function (e.g., hemoglobin \>10 g/dl, white blood count 3600-11,000mm3, absolute granulocyte count ≥1,500/mm3, absolute lymphocyte count ≥1,000/mm3, and platelet count ≥100K/mm3. Eligibility level of hemoglobin can be reached by transfusion.
* Adequate liver function (SGPT, SGOT, and alkaline phosphatase ≤1.5 times upper limits of normals (ULN) and total bilirubin ≤1.5mg/dl), and adequate renal function (BUN or creatinine ≤1.5 times ULN) prior to starting therapy.

Brain and Nervous System

IU Health Arnett

• IU Health Arnett Hospital

• IU Health Methodist Hospital
• Indiana University Hospital / IU Simon Cancer Center

• First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma
  Liau LM;Ashkan K;Tran DD;Campian JL;Trusheim JE;Cobbs CS;Heth JA;Salacz M;Taylor S;D'Andre SD;Iwamoto FM;Dropcho EJ;Moshel YA;Walter KA;Pillainayagam CP;Aiken R;Chaudhary R;Goldlust SA;Bota DA;Duic P;Grewal J;Elinzano H;Toms SA;Lillehei KO;Mikkelsen T;Walbert T;Abram SR;Brenner AJ;Brem S;Ewend MG;Khagi S;Portnow J;Kim LJ;Loudon WG;Thompson RC;Avigan DE;Fink KL;Geoffroy FJ;Lindhorst S;Lutzky J;Sloan AE;Schackert G;Krex D;Meisel HJ;Wu J;Davis RP;Duma C;Etame AB;Mathieu D;Kesari S;Piccioni D;Westphal M;Baskin DS;New PZ;Lacroix M;May SA;Pluard TJ;Tse V;Green RM;Villano JL;Pearlman M;Petrecca K;Schulder M;Taylor LP;Maida AE;Prins RM;Cloughesy TF;Mulholland P;Bosch ML;
• Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial
  Liau LM;Ashkan K;Brem S;Campian JL;Trusheim JE;Iwamoto FM;Tran DD;Ansstas G;Cobbs CS;Heth JA;Salacz ME;D'Andre S;Aiken RD;Moshel YA;Nam JY;Pillainayagam CP;Wagner SA;Walter KA;Chaudhary R;Goldlust SA;Lee IY;Bota DA;Elinzano H;Grewal J;Lillehei K;Mikkelsen T;Walbert T;Abram S;Brenner AJ;Ewend MG;Khagi S;Lovick DS;Portnow J;Kim L;Loudon WG;Martinez NL;Thompson RC;Avigan DE;Fink KL;Geoffroy FJ;Giglio P;Gligich O;Krex D;Lindhorst SM;Lutzky J;Meisel HJ;Nadji-Ohl M;Sanchin L;Sloan A;Taylor LP;Wu JK;Dunbar EM;Etame AB;Kesari S;Mathieu D;Piccioni DE;Baskin DS;Lacroix M;May SA;New PZ;Pluard TJ;Toms SA;Tse V;Peak S;Villano JL;Battiste JD;Mulholland PJ;Pearlman ML;Petrecca K;Schulder M;Prins RM;Boynton AL;Bosch ML;
• Clinical trials in cellular immunotherapy for brain/CNS tumors
  Badhiwala J;Decker WK;Berens ME;Bhardwaj RD;