Clinical trial NCT00045968: Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer
Official title: A Phase III Clinical Trial Evaluating DCVax®-L, Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen For The Treatment Of Glioblastoma Multiforme (GBM)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Glioblastoma
GBM
Grade IV Astrocytoma
Glioma
Brain Cancer
Brain Tumor
Keywords: oncology
neurology
glioma
brain tumor
brain cancer
glioblastoma multiforme
glioblastoma
newly diagnosed glioblastoma
immunotherapy
dendritic cells
immune therapy
GBM
Brain cancer, primary
tumor vaccine
grade IV astrocytoma
DCVax
Grade IV brain cancer
Lead sponsor: Northwest Biotherapeutics
Sponsor class: INDUSTRY
First posted: 2002-09-19
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to determine the efficacy of an investigational therapy called DCVax(R)-L in patients with newly diagnosed GBM for whom surgery is indicated. Patients must enter screening at a participating site prior to surgical resection of the tumor. Patients will receive the standard of care, including radiation and Temodar therapy and two out of three will additionally receive DCVax-L, with the remaining one third receiving a placebo. All patients will have the option to receive DCVax-L in a crossover arm upon documented disease progression. (note: DCVax-L when used for patients with brain cancer is sometimes also referred to as DCVax-Brain)

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary objective of this study is to compare overall survival (OS) between patients randomized to DCVax-L and control patients from comparable, contemporaneous trials who received standard of care therapy only, in newly diagnosed glioblastoma.
timeFrame: Until death
Secondary outcomes:
measure: The first secondary objective is to compare overall survival (OS) between patients randomized to placebo who received DCVax-L treatment following disease recurrence, and control patients from comparable, contemporaneous clinical trials, in recurrent GBM.
timeFrame: Until death
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Castro Valley
country: United States
facility: Sutter East Bay Neuroscience Institute-Eden Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente - Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Orange
country: United States
facility: St. Joseph Hospital of Orange
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente - Redwood City
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Community Clinical Oncology Program
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Warrenville
country: United States
facility: Cadence Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center/University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: John Nasseff Neuroscience Institute at Abbott Northwestern Hospital
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Edison
country: United States
facility: The Brain Tumor Center at JFK Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Trenton
country: United States
facility: Capital Health Regional Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Long Island Brain Tumor Center at Neurological Surgery, P.C.
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: New York University Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
city: White Plains
country: United States
facility: Brain and Spine Surgeons of New York and Northern Westchester Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Science Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Hospital for Neuroscience
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina Hospitals and Clinics
state: South Carolina
city: Nashville
country: United States
facility: Saint Thomas Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research at University of Texas Health Science Center San Antonio
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Seattle
country: United States
facility: Swedish Hospital Neuroscience Research
state: Washington
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Montreal
country: Canada
facility: Montreal Neurological Institute, McGill University
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS - Hôpital Fleurimont
state: Quebec
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg Neurochirurgische Klinik
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Katharinenhospital
state: Baden-Württemberg
city: Frankfurt
country: Germany
facility: Universitätsklinikum FrankfurtKlinik und Poliklinik für Neurochirurgie
state: Hesse
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn Nervenklinik (Zentrum), Klinik und Poliklinik für Neurochirurgie
state: North Rhine-Westphalia
city: Köln
country: Germany
facility: Universitätsklinikum Klinik für allgemeine Neurochirurgie
state: North Rhine-Westphalia
city: Halle
country: Germany
facility: BG-Kliniken Bergmannstrost, Klinik für Neurochirurgie
state: Saxony-Anhalt
city: Chemnitz
country: Germany
facility: Klinik für Neurochirurgie, Klinikum Chemnitz gGmbH
state: Saxony
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
state: Saxony
city: Hamburg
country: Germany
facility: Neurochirurgische Klinik
city: Cambridge
country: United Kingdom
facility: Addenbrookes NHS Trust
state: Cambridgeshire, East Anglia
city: London
country: United Kingdom
facility: Kings College Hosital NHS Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: University College Hospital London
state: Greater London
city: Birmingham
country: United Kingdom
facility: University Hospital of Birmingham NHS Foundation Trust
state: West Midlands
Study officials:
affiliation: University of California, Los Angeles
name: Linda Liau, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwest Biotherapeutics
name: Marnix L. Bosch, MBA, PhD
role: STUDY_DIRECTOR
References:
citation: 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. 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. JAMA Oncol. 2023 Jan 1;9(1):112-121. doi: 10.1001/jamaoncol.2022.5370.
citation: 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. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018 May 29;16(1):142. doi: 10.1186/s12967-018-1507-6.
citation: Badhiwala J, Decker WK, Berens ME, Bhardwaj RD. Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 2013 Apr;13(4):405-24. doi: 10.1586/ern.13.23.