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

NCT ID: NCT00045968

Last Updated: 2022-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

348 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-12-31

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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treatment cohort

Group Type ACTIVE_COMPARATOR

Dendritic cell immunotherapy

Intervention Type DRUG

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.

Placebo Chohort

Autologous PBMC

Group Type PLACEBO_COMPARATOR

Dendritic cell immunotherapy

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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DCVax-L DCVax DCVax-Brain

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northwest Biotherapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Linda Liau, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Marnix L. Bosch, MBA, PhD

Role: STUDY_DIRECTOR

Northwest Biotherapeutics

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Sutter East Bay Neuroscience Institute-Eden Medical Center

Castro Valley, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

UCSD Moores Cancer Center

La Jolla, California, United States

Site Status

Kaiser Permanente - Los Angeles

Los Angeles, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

St. Joseph Hospital of Orange

Orange, California, United States

Site Status

University of California, Irvine Medical Center

Orange, California, United States

Site Status

Kaiser Permanente - Redwood City

Redwood City, California, United States

Site Status

Sutter Institute for Medical Research

Sacramento, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Colorado Neurological Institute

Englewood, Colorado, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Memorial Cancer Institute

Hollywood, Florida, United States

Site Status

Mount Sinai Community Clinical Oncology Program

Miami Beach, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Illinois Cancer Care

Peoria, Illinois, United States

Site Status

Cadence Cancer Center

Warrenville, Illinois, United States

Site Status

IU Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Markey Cancer Center/University of Kentucky

Lexington, Kentucky, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

John Nasseff Neuroscience Institute at Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

St. Luke's Hospital

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

The Brain Tumor Center at JFK Medical Center

Edison, New Jersey, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

The Valley Hospital

Ridgewood, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

Site Status

Capital Health Regional Medical Center

Trenton, New Jersey, United States

Site Status

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

Lake Success, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

New York University Clinical Cancer Center

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Stony Brook Medicine

Stony Brook, New York, United States

Site Status

Brain and Spine Surgeons of New York and Northern Westchester Hospital

White Plains, New York, United States

Site Status

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

OhioHealth

Columbus, Ohio, United States

Site Status

Oklahoma University Health Science Center

Oklahoma City, Oklahoma, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Jefferson Hospital for Neuroscience

Philadelphia, Pennsylvania, United States

Site Status

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina Hospitals and Clinics

Charleston, South Carolina, United States

Site Status

Saint Thomas Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Baylor Research Institute

Dallas, Texas, United States

Site Status

The Methodist Hospital

Houston, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

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

San Antonio, Texas, United States

Site Status

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States

Site Status

Swedish Hospital Neuroscience Research

Seattle, Washington, United States

Site Status

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Montreal Neurological Institute, McGill University

Montreal, Quebec, Canada

Site Status

CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

Universitätsklinikum Heidelberg Neurochirurgische Klinik

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Katharinenhospital

Stuttgart, Baden-Wurttemberg, Germany

Site Status

Universitätsklinikum FrankfurtKlinik und Poliklinik für Neurochirurgie

Frankfurt am Main, Hesse, Germany

Site Status

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

Bonn, North Rhine-Westphalia, Germany

Site Status

Universitätsklinikum Klinik für allgemeine Neurochirurgie

Cologne, North Rhine-Westphalia, Germany

Site Status

Klinik für Neurochirurgie, Klinikum Chemnitz gGmbH

Chemnitz, Saxony, Germany

Site Status

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Saxony, Germany

Site Status

BG-Kliniken Bergmannstrost, Klinik für Neurochirurgie

Halle, Saxony-Anhalt, Germany

Site Status

Neurochirurgische Klinik

Hamburg, , Germany

Site Status

Addenbrookes NHS Trust

Cambridge, Cambridgeshire, East Anglia, United Kingdom

Site Status

Kings College Hosital NHS Foundation Trust

London, Greater London, United Kingdom

Site Status

University College Hospital London

London, Greater London, United Kingdom

Site Status

University Hospital of Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom

Site Status

Countries

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United States Canada Germany United Kingdom

References

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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.

Reference Type DERIVED
PMID: 36394838 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29843811 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23545055 (View on PubMed)

Related Links

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http://www.nwbio.com

Northwest Biotherapeutics, Inc.

Other Identifiers

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020221

Identifier Type: -

Identifier Source: org_study_id

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