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

Sponsor:	Northwest Biotherapeutics
Information provided by (Responsible Party):	Northwest Biotherapeutics
ClinicalTrials.gov Identifier:	NCT00045968

Purpose

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. Patients randomized to the placebo arm 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	Intervention	Phase
Glioblastoma Multiforme Glioblastoma GBM Grade IV Astrocytoma Glioma Brain Cancer Brain Tumor	Drug: Dendritic cell immunotherapy	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

U.S. FDA Resources

Further study details as provided by Northwest Biotherapeutics:

Primary Outcome Measures:

The primary objective of this study is to compare progression free survival from time of randomization between patients treated with DCVax-L and control patients. [ Time Frame: Time to tumor progression or death ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The secondary objective is to compare overall survival and time to disease progression between DCVax-L treated and control patients. [ Time Frame: Until Death ] [ Designated as safety issue: No ]

Estimated Enrollment:	300
Study Start Date:	December 2006
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Detailed Description:

This Phase III trial is designed to evaluate the impact on disease progression and 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 PFS (progression free survival), and the first secondary endpoint is overall survival (OS). Other endpoints include performance status, immune response, and also safety. Interim analyses to assess efficacy are incorporated in the trial design.

Side effects reported from early trials are mostly mild, and may include skin reactions of redness, pain & swelling at the injection site.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045968

Contacts

Contact: Marnix L Bosch, MBA, PhD

240-497-9022

marnix@nwbio.com

Show 42 Study Locations

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. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Northwest Biotherapeutics
ClinicalTrials.gov Identifier:	NCT00045968 History of Changes
Other Study ID Numbers:	020221
Study First Received:	September 17, 2002
Last Updated:	May 17, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Northwest Biotherapeutics:

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
DCVax
Grade IV brain cancer

Additional relevant MeSH terms:

Astrocytoma
Brain Neoplasms
Glioblastoma
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

ClinicalTrials.gov processed this record on May 21, 2012