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

Phase 3

• Conditions: Grade IV Astrocytoma; Brain Cancer; Glioblastoma; Glioma; Brain Tumor; Glioblastoma Multiforme; GBM
• Interventions: Drug: Dendritic cell immunotherapy

• Registration Number: NCT00045968
• Lead Sponsor: Northwest Biotherapeutics

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 Timeline

• Study First Submitted: 2002-09-17
• Study First Submitted QC: 2002-09-18
• Study First Posted: 2002-09-19
• Study Start: 2006-12
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-12
• Last Update Posted: 2022-05-18
• Primary Completion: 2022-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 348

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
treatment cohort	Dendritic cell immunotherapy	-
Placebo Chohort	Dendritic cell immunotherapy	Autologous PBMC

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (86)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Sutter East Bay Neuroscience Institute-Eden Medical Center; 🇺🇸 Castro Valley, California, United States

City of Hope; 🇺🇸 Duarte, California, United States

UCSD Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Kaiser Permanente - Los Angeles; 🇺🇸 Los Angeles, California, United States

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

St. Joseph Hospital of Orange; 🇺🇸 Orange, California, United States

University of California, Irvine Medical Center; 🇺🇸 Orange, California, United States

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