Daclizumab in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused Lymphopenia - Full Text View

Sponsors and Collaborators:	Duke University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00626483

Purpose

RATIONALE: Monoclonal antibodies, such as daclizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vaccines may help the body build an effective immune response to kill tumor cells. Giving these treatments together may kill more tumor cells.

PURPOSE: This clinical trial is studying how well daclizumab works in treating patients with newly diagnosed glioblastoma multiforme and temozolomide-caused lymphopenia who are undergoing targeted immunotherapy.

Condition	Intervention
Brain and Central Nervous System Tumors	Drug: RNA-loaded dendritic cell vaccine Drug: cytomegalovirus pp65-specific cytotoxic T lymphocytes Drug: daclizumab Drug: imiquimod Drug: temozolomide Drug: therapeutic autologous dendritic cells Drug: therapeutic autologous lymphocytes Procedure: radionuclide imaging Procedure: single photon emission computed tomography Procedure: stereotactic radiation therapy

MedlinePlus related topics: Cancer Cytomegalovirus Infections Nuclear Scans

Drug Information available for: Temozolomide S 26308 Dacliximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	REGULATory T-Cell Inhibition With Daclizumab (Zenapax®) During Recovery From Therapeutic Temozolomide-Induced Lymphopenia During Antitumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed Glioblastoma Multiforme [REGULATe]

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Functional capacity of CD4+,CD25+, CD127- T-regulatory cells [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	6
Study Start Date:	March 2007
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine if daclizumab inhibits the functional and numeric recovery of T-regulatory cells after therapeutic temozolomide (TMZ)-induced lymphopenia in the context of vaccinating adult patients with newly diagnosed glioblastoma multiforme (GBM) using cytomegalovirus (CMV) pp65-lysosomal-associated membrane protein (LAMP) mRNA-loaded dendritic cells (DCs) with autolymphocyte therapy (ALT) in patients who are seropositive and seronegative for CMV.

Secondary

To evaluate the safety of daclizumab in these patients.
To determine if daclizumab enhances the magnitude or character of pp65-specific vaccine-induced cellular or humoral immune responses, inhibits or enhances activation-induced cell death, or induces immunologic or clinical evidence of autoimmunity.
To determine if daclizumab alters the phenotype (CD56 expression), cytokine secretion profile, or cytotoxicity of CD3-CD56+ natural killer cells.
To determine if daclizumab in addition to vaccination and ALT extends progression-free survival compared to historical cohorts.
To assess the differential ability of indium In 111-labeled DCs to track to the inguinal lymph nodes under different skin-preparative conditions.
To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of antigen-escape outgrowth.

OUTLINE: Patients undergo leukapheresis for generation of dendritic cells (DCs) and autolymphocyte therapy (ALT) within 4 weeks after resection. After initial leukapheresis, all patients undergo stereotactic radiotherapy (RT) on days 1-5 and concurrent temozolomide (TMZ) IV on days 1-7 for 6.5 weeks in the absence of disease progression or unacceptable toxicity.

Beginning 3 weeks after completion of RT, patients receive TMZ IV on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 21 of the first course of TMZ, patients receive pp65-LAMP mRNA-loaded mature DCs every 2 weeks for 3 vaccinations. Concurrently with the first DC vaccination, patients receive ALT IV over 15 minutes and daclizumab IV over 15 minutes.

On day 21 of the second course of post-radiation TMZ, patients receive indium In 111-labeled DCs (fourth vaccination) and randomly assigned skin preparations (unpulsed DCs vs imiquimod cream applied to the vaccination site 6-24 hours before vaccination). Single-photon emission computed tomography (SPECT) images are used to quantitate migration to the inguinal lymph nodes.

After completion of study treatment, patients are followed every 2 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histopathologically confirmed glioblastoma multiforme
- WHO grade IV disease
Must undergo leukapheresis ≤ 4 weeks after definitive resection
Residual radiographic contrast enhancement on post-resection CT scan or MRI must not exceed 1 cm in diameter in two perpendicular axial planes
- Patients with evidence of contrast enhancement exceeding 1 cm in diameter in two perpendicular axial planes after radiation will not be a candidate for the vaccine despite being previously enrolled and will be removed from the study and replaced
No radiographic or cytologic evidence of leptomeningeal or multicentric disease

PATIENT CHARACTERISTICS:

Karnofsky performance status 80-100%
Curran Group status I-IV
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infection requiring treatment
No unexplained febrile (>101.5°F) illness
No known immunosuppressive disease or known HIV infection
No unstable or severe intercurrent medical conditions such as severe heart or lung disease
No allergy to temozolomide (TMZ) or otherwise unable to tolerate TMZ for reasons other than lymphopenia
- Patients who are found after enrollment to be unable to tolerate TMZ will not be a candidate for the vaccine despite being previously enrolled and will be removed from the study and replaced
No prior allergic reaction to daclizumab or one of its components

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior daclizumab
No other prior conventional therapeutic intervention except for steroids, radiation, or temozolomide
No prior inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies
No concurrent corticosteroids, with the exception of nasal or inhaled steroids, at a dose above physiologic levels
- Patients requiring an increase in corticosteroids, with the exception of nasal or inhaled steroids, such that at the time of first vaccination they require a dose above physiologic levels, will be removed from the study and replaced (physiologic dose will be defined as < 2 mg of dexamethasone/day)
- Once vaccinations have been initiated, if patients subsequently require increased steroids, they will still be permitted to remain on the study, but every effort will be made to minimize steroid requirements
No prior allogeneic solid organ transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626483

Locations

United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

National Cancer Institute (NCI)

Investigators

Study Chair:

Duane Mitchell, MD, PhD

Duke University

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000579683, DUMC-PRO00000581, SPORE Project 3
Study First Received:	February 28, 2008
Last Updated:	December 27, 2008
ClinicalTrials.gov Identifier:	NCT00626483
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Hematologic Diseases
Daclizumab
Lymphopenia
Imiquimod
Leukocyte Disorders
Central Nervous System Neoplasms
Temozolomide
Cytomegalovirus
Immunologic Deficiency Syndromes

Neuroectodermal Tumors
Glioblastoma multiforme
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Cytomegalovirus Infections
Glioma
Gliosarcoma
Leukopenia
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Nervous System Diseases

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009