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

Tracking Information

• First Submitted Date: September 17, 2002
• First Posted Date: September 19, 2002
• Last Update Posted Date: May 18, 2022
• Study Start Date: December 2006
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 12, 2022): 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 ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: May 12, 2022): 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 ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

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.

Other Names:

• DCVax-L
• DCVax
• DCVax-Brain

Study Arms

• Active Comparator: treatment cohort
  Intervention: Drug: Dendritic cell immunotherapy
• Placebo Comparator: Placebo Chohort
  Autologous PBMC
  Intervention: Drug: Dendritic cell immunotherapy

Publications *

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 8, 2015): 348
• Original Enrollment (submitted: June 23, 2005): 90
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United Kingdom, United States

Administrative Information

• NCT Number: NCT00045968
• Other Study ID Numbers: 020221
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Northwest Biotherapeutics
• Original Responsible Party: Not Provided
• Current Study Sponsor: Northwest Biotherapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Northwest Biotherapeutics
• Verification Date: May 2022