Basiliximab in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused Lymphopenia (REGULATe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00626483
Recruitment Status : Active, not recruiting
First Posted : February 29, 2008
Last Update Posted : May 17, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University

Brief Summary:

RATIONALE: Monoclonal antibodies, such as basiliximab, 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. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) is a powerful adjuvant capable of stimulating macrophage function, inducing proliferation and maturation of DCs, and is able to enhance T-lymphocyte stimulatory function. Intradermal administration of GM-CSF enhances the immunization efficacy at the site of administration

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

Condition or disease Intervention/treatment Phase
Malignant Neoplasms Brain Biological: RNA-loaded dendritic cell vaccine Drug: basiliximab Phase 1

Detailed Description:



  • To determine if basiliximab 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 GM-CSF in patients who are seropositive and seronegative for CMV.


  • To evaluate the safety of basiliximab in these patients.
  • To determine if basiliximab 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 basiliximab alters the phenotype (CD56 expression), cytokine secretion profile, or cytotoxicity of CD3-CD56+ natural killer cells.
  • To determine if basiliximab in addition to vaccination extends progression-free survival compared to historical cohorts.
  • 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) 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 12 courses in the absence of disease progression or unacceptable toxicity. On day 14 ± 2 days of this first cycle of TMZ, patients will receive basiliximab, which is 7 days (± 2 days) before DC vaccine #1 and 2 weeks later, a second dose of basiliximab will be given, which is also 7 days before vaccine # 2.

All patients will undergo leukapheresis again for DC generation and immunologic monitoring with specific assessment of baseline antigen-specific cellular and humoral immune responses 3 + 1 weeks after vaccine #3.

Patients will then be treated monthly with TMZ cycles for a total of 12 cycles . On day 21 ± 2 days of each TMZ cycle, patients will receive monthly vaccines for a total of 8 vaccines. Patients will have blood drawn for immunologic monitoring before basiliximab infusions and prior to vaccines 1, 2, 3, and prior to monthly vaccines and then bimonthly through TMZ cycles without receiving any other prescribed antitumor therapy until progression.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: REGULATory T-Cell Inhibition With Basiliximab (Simulect®) During Recovery From Therapeutic Temozolomide-induced Lymphopenia During Antitumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed Glioblastoma Multiforme
Study Start Date : March 2007
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : June 2019

Arm Intervention/treatment
Experimental: CMV pp65-LAMP mRNA-loaded DC vaccination
Basiliximab will be safe in combination with CMV pp65-LAMP mRNA-loaded DC vaccination and GM-CSF
Biological: RNA-loaded dendritic cell vaccine
Only one dose of DCs (2 x 10^7) is being assessed.

Drug: basiliximab
Basiliximab 20 mg and 40 mg is being assessed depending on dose-cohort enrollment.

Primary Outcome Measures :
  1. Functional capacity of CD4+,CD25+, CD127- T-regulatory cells [ Time Frame: Approximately 26 months at time of brain tumor progression ]
    Functional and quantitative recovery of regulatory T cells is measured during and following study treatment and at the time of tumor progression, which is estimated to be about 26 months from time of diagnosis based on expected progression free survival rates with standard of care therapy.

Secondary Outcome Measures :
  1. Safety [ Time Frame: 2 months following last vaccine administration ]
    The safety of CMV pulsed pp65 DC Vaccines combined with basiliximab is measured based on adverse events considered related to study treatment.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00626483

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Gary Archer Ph.D.
National Cancer Institute (NCI)
Principal Investigator: Dina Randazzo, DO Duke University

Publications of Results:
Responsible Party: Gary Archer Ph.D., Assistant Professor Neurosurgery, Duke University Identifier: NCT00626483     History of Changes
Other Study ID Numbers: Pro00000581
P50CA108786 ( U.S. NIH Grant/Contract )
P30CA014236 ( U.S. NIH Grant/Contract )
SPORE Project 3
CDR0000579683 ( Other Identifier: National Cancer Institute )
First Posted: February 29, 2008    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018

Keywords provided by Gary Archer Ph.D., Duke University:
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs