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

NCT00626483 | Completed Phase 1 DMC

• 5 other identifiers: Pro00000581P50CA108786P30CA014236SPORE Project 3CDR0000579683
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Neoplasms Brain

Keywords

adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Functional capacity of CD4+,CD25+, CD127- T-regulatory cells

  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.

  Approximately 26 months at time of brain tumor progression

Secondary Outcomes (5)

• Safety of CMV pulsed pp65 DC vaccines

  2 months following last vaccine administration

• Effect of basilixiumab on pp65 vaccine

  1 year

• Effect of basilixiumab on immune profiles

  1 year

• Progression-free survival (PFS)

  1 year

• Characterize immune cells in recurrent tumors

  1 year

Study Arms (1)

CMV pp65-LAMP mRNA-loaded DC vaccination

EXPERIMENTAL

Basiliximab will be safe in combination with CMV pp65-LAMP mRNA-loaded DC vaccination and GM-CSF

Biological: RNA-loaded dendritic cell vaccine; Drug: basiliximab

Interventions

RNA-loaded dendritic cell vaccine BIOLOGICAL

Only one dose of DCs (2 x 10\^7) is being assessed.

CMV pp65-LAMP mRNA-loaded DC vaccination

basiliximab DRUG

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

CMV pp65-LAMP mRNA-loaded DC vaccination

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Gary Archer Ph.D.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Mitchell DA, Cui X, Schmittling RJ, Sanchez-Perez L, Snyder DJ, Congdon KL, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH. Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood. 2011 Sep 15;118(11):3003-12. doi: 10.1182/blood-2011-02-334565. Epub 2011 Jul 18.

  PMID: 21768296 RESULT

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Basiliximab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mustafa Khasraw, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor Neurosurgery

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: February 29, 2008
• Study Start: April 24, 2007
• Primary Completion: July 6, 2016
• Study Completion: July 6, 2016
• Last Updated: March 9, 2021

Record last verified: 2021-03

Locations

US (1)