Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer

Glioblastoma Clinical Trial

— GBM  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00045968
• Other study ID #: 020221
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2006

Study information

• Verified date: May 2022
• Source: Northwest Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 348
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Astrocytoma
• Brain Cancer
• Brain Neoplasms
• Brain Tumor
• GBM
• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• Grade IV Astrocytoma

Intervention

Drug:
• Dendritic cell immunotherapy
Two intradermal (i.d.) injections of DCVax-L(treatment cohort) or autologous PBMC (placebo cohort) per treatment. Treatments will be given at days 0, 10, 20, and at weeks 8, 16, 32, 48, 72, 96 and 120.

Locations

Country	Name	City	State
Canada	Montreal Neurological Institute, McGill University	Montreal	Quebec
Canada	CHUS - Hôpital Fleurimont	Sherbrooke	Quebec
Germany	Universitätsklinikum Bonn Nervenklinik (Zentrum), Klinik und Poliklinik für Neurochirurgie	Bonn	North Rhine-Westphalia
Germany	Klinik für Neurochirurgie, Klinikum Chemnitz gGmbH	Chemnitz	Saxony
Germany	Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden	Saxony
Germany	Universitätsklinikum FrankfurtKlinik und Poliklinik für Neurochirurgie	Frankfurt	Hesse
Germany	BG-Kliniken Bergmannstrost, Klinik für Neurochirurgie	Halle	Saxony-Anhalt
Germany	Neurochirurgische Klinik	Hamburg
Germany	Universitätsklinikum Heidelberg Neurochirurgische Klinik	Heidelberg	Baden-Württemberg
Germany	Universitätsklinikum Klinik für allgemeine Neurochirurgie	Köln	North Rhine-Westphalia
Germany	Katharinenhospital	Stuttgart	Baden-Württemberg
United Kingdom	University Hospital of Birmingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	Addenbrookes NHS Trust	Cambridge	Cambridgeshire, East Anglia
United Kingdom	Kings College Hosital NHS Foundation Trust	London	Greater London
United Kingdom	University College Hospital London	London	Greater London
United States	University of Michigan Cancer Center	Ann Arbor	Michigan
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Sutter East Bay Neuroscience Institute-Eden Medical Center	Castro Valley	California
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina Hospitals and Clinics	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	OhioHealth	Columbus	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	The Brain Tumor Center at JFK Medical Center	Edison	New Jersey
United States	Colorado Neurological Institute	Englewood	Colorado
United States	University of Florida	Gainesville	Florida
United States	Spectrum Health	Grand Rapids	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Cancer Institute	Hollywood	Florida
United States	The Methodist Hospital	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	IU Simon Cancer Center	Indianapolis	Indiana
United States	St. Luke's Hospital	Kansas City	Missouri
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Long Island Brain Tumor Center at Neurological Surgery, P.C.	Lake Success	New York
United States	Markey Cancer Center/University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Kaiser Permanente - Los Angeles	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	Mount Sinai Community Clinical Oncology Program	Miami Beach	Florida
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	John Nasseff Neuroscience Institute at Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Saint Thomas Research Institute	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York University Clinical Cancer Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Oklahoma University Health Science Center	Oklahoma City	Oklahoma
United States	St. Joseph Hospital of Orange	Orange	California
United States	University of California, Irvine Medical Center	Orange	California
United States	Illinois Cancer Care	Peoria	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Jefferson Hospital for Neuroscience	Philadelphia	Pennsylvania
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Kaiser Permanente - Redwood City	Redwood City	California
United States	The Valley Hospital	Ridgewood	New Jersey
United States	University of Rochester Medical Center	Rochester	New York
United States	Sutter Institute for Medical Research	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Therapy & Research at University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington
United States	Swedish Hospital Neuroscience Research	Seattle	Washington
United States	Stony Brook Medicine	Stony Brook	New York
United States	Overlook Hospital	Summit	New Jersey
United States	Moffitt Cancer Center	Tampa	Florida
United States	Capital Health Regional Medical Center	Trenton	New Jersey
United States	Cadence Cancer Center	Warrenville	Illinois
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Brain and Spine Surgeons of New York and Northern Westchester Hospital	White Plains	New York
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Northwest Biotherapeutics

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Until death
Secondary	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.		Until death

External Links

•   Northwest Biotherapeutics, Inc.