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

• ClinicalTrials.gov Identifier: NCT00045968
• Recruitment Status: Active, not recruiting
• First Posted: September 19, 2002
• Last Update Posted: May 18, 2022
• Sponsor: Northwest Biotherapeutics
• Information provided by (Responsible Party): Northwest Biotherapeutics

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme; Glioblastoma; GBM; Grade IV Astrocytoma; Glioma; Brain Cancer; Brain Tumor	Drug: Dendritic cell immunotherapy	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 348 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2006
• Estimated Primary Completion Date: November 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: treatment cohort	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.; Other Names: DCVax-L; DCVax; DCVax-Brain
Placebo Comparator: Placebo Chohort; Autologous PBMC	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.; Other Names: DCVax-L; DCVax; DCVax-Brain

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Until death ]

Secondary Outcome Measures :

1. 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. [ Time Frame: Until death ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Sutter East Bay Neuroscience Institute-Eden Medical Center

Castro Valley, California, United States, 94546

City of Hope

Duarte, California, United States, 91010

UCSD Moores Cancer Center

La Jolla, California, United States, 93093

Kaiser Permanente - Los Angeles

Los Angeles, California, United States, 90027

UCLA Medical Center

Los Angeles, California, United States, 90095

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

St. Joseph Hospital of Orange

Orange, California, United States, 92868

University of California, Irvine Medical Center

Orange, California, United States, 92868

Kaiser Permanente - Redwood City

Redwood City, California, United States, 94063

Sutter Institute for Medical Research

Sacramento, California, United States, 95816

United States, Colorado

University of Colorado Cancer Center

Aurora, Colorado, United States, 80045

Colorado Neurological Institute

Englewood, Colorado, United States, 80113

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20057

United States, Florida

University of Florida

Gainesville, Florida, United States, 32611

Memorial Cancer Institute

Hollywood, Florida, United States, 33021

Mount Sinai Community Clinical Oncology Program

Miami Beach, Florida, United States, 33140

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Piedmont Atlanta Hospital

Atlanta, Georgia, United States, 30309

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

Illinois Cancer Care

Peoria, Illinois, United States, 61615

Cadence Cancer Center

Warrenville, Illinois, United States, 60555

United States, Indiana

IU Simon Cancer Center

Indianapolis, Indiana, United States, 46202

United States, Kansas

University of Kansas Cancer Center

Westwood, Kansas, United States, 66205

United States, Kentucky

Markey Cancer Center/University of Kentucky

Lexington, Kentucky, United States, 40536

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan Cancer Center

Ann Arbor, Michigan, United States, 48109

Henry Ford Hospital

Detroit, Michigan, United States, 48202

Spectrum Health

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

John Nasseff Neuroscience Institute at Abbott Northwestern Hospital

Minneapolis, Minnesota, United States, 55407

United States, Missouri

St. Luke's Hospital

Kansas City, Missouri, United States, 64111

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

The Brain Tumor Center at JFK Medical Center

Edison, New Jersey, United States, 08818

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

The Valley Hospital

Ridgewood, New Jersey, United States, 07450

Overlook Hospital

Summit, New Jersey, United States, 07902

Capital Health Regional Medical Center

Trenton, New Jersey, United States, 08638

United States, New York

Long Island Brain Tumor Center at Neurological Surgery, P.C.

Lake Success, New York, United States, 11042

North Shore University Hospital

Manhasset, New York, United States, 11030

New York University Clinical Cancer Center

New York, New York, United States, 10016

Mount Sinai Medical Center

New York, New York, United States, 10029-6574

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester Medical Center

Rochester, New York, United States, 14642

Stony Brook Medicine

Stony Brook, New York, United States, 11794

Brain and Spine Surgeons of New York and Northern Westchester Hospital

White Plains, New York, United States, 10604

United States, North Carolina

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States, 27514

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States, 45267

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States, 44106

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Ohio State University

Columbus, Ohio, United States, 43210

OhioHealth

Columbus, Ohio, United States, 43214

United States, Oklahoma

Oklahoma University Health Science Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Geisinger Medical Center

Danville, Pennsylvania, United States, 17822

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Jefferson Hospital for Neuroscience

Philadelphia, Pennsylvania, United States, 19107

Temple University School of Medicine

Philadelphia, Pennsylvania, United States, 19140

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Medical University of South Carolina Hospitals and Clinics

Charleston, South Carolina, United States, 29425

United States, Tennessee

Saint Thomas Research Institute

Nashville, Tennessee, United States, 37205

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor Research Institute

Dallas, Texas, United States, 75246

The Methodist Hospital

Houston, Texas, United States, 77030

University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

Cancer Therapy & Research at University of Texas Health Science Center San Antonio

San Antonio, Texas, United States, 78229

United States, Washington

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States, 98101

Swedish Hospital Neuroscience Research

Seattle, Washington, United States, 98122

United States, Wisconsin

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States, 23215

Canada, Quebec

Montreal Neurological Institute, McGill University

Montreal, Quebec, Canada, H3A 2B4

CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, Canada, J1H 5N4

Germany

Universitätsklinikum Heidelberg Neurochirurgische Klinik

Heidelberg, Baden-Württemberg, Germany, 69120

Katharinenhospital

Stuttgart, Baden-Württemberg, Germany, 70174

Universitätsklinikum FrankfurtKlinik und Poliklinik für Neurochirurgie

Frankfurt, Hesse, Germany, 60528

Universitätsklinikum Bonn Nervenklinik (Zentrum), Klinik und Poliklinik für Neurochirurgie

Bonn, North Rhine-Westphalia, Germany, 53105

Universitätsklinikum Klinik für allgemeine Neurochirurgie

Köln, North Rhine-Westphalia, Germany, 50924

BG-Kliniken Bergmannstrost, Klinik für Neurochirurgie

Halle, Saxony-Anhalt, Germany, 06112

Klinik für Neurochirurgie, Klinikum Chemnitz gGmbH

Chemnitz, Saxony, Germany, 09116

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Saxony, Germany, 01307

Neurochirurgische Klinik

Hamburg, Germany, 20246

United Kingdom

Addenbrookes NHS Trust

Cambridge, Cambridgeshire, East Anglia, United Kingdom, CB2 2QQ

Kings College Hosital NHS Foundation Trust

London, Greater London, United Kingdom, SE5 9RS

University College Hospital London

London, Greater London, United Kingdom, WC1E 6BT

University Hospital of Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom, N15 2WB

Sponsors and Collaborators

Northwest Biotherapeutics

Investigators

• Principal Investigator: Linda Liau, M.D.; University of California, Los Angeles
• Study Director: Marnix L. Bosch, MBA, PhD; Northwest Biotherapeutics

More Information

Additional Information:

Northwest Biotherapeutics, Inc. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Erratum In: J Transl Med. 2018 Jun 29;16(1):179.

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.

• Responsible Party: Northwest Biotherapeutics
• ClinicalTrials.gov Identifier: NCT00045968
• Other Study ID Numbers: 020221
• First Posted: September 19, 2002
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

Keywords provided by Northwest Biotherapeutics:

DCVax; 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; Grade IV brain cancer

Additional relevant MeSH terms:

Glioblastoma; Brain Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases