Trial record 3 of 10 for:    Lymphocytopenia | Open Studies | NIH, U.S. Fed

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John Sampson, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00626483
First received: February 28, 2008
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Malignant Neoplasms Brain
Biological: RNA-loaded dendritic cell vaccine
Drug: basiliximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Functional capacity of CD4+,CD25+, CD127- T-regulatory cells [ Time Frame: 26 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Time Frame: 26 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: March 2007
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Denise Lally-Goss, RN, MSN, NP    919-684-3862    lally001@mc.duke.edu   
Contact: Sharon Norman, C.R.C.    919-668-2696    sharon.mcgehee@duke.edu   
Principal Investigator: Gordana Vlahovic, M.D.         
Sponsors and Collaborators
John Sampson
Investigators
Principal Investigator: Gordana Vlahovic, MD Duke University
  More Information

Additional Information:
Publications:
Responsible Party: John Sampson, Professor Neurosurgery, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00626483     History of Changes
Other Study ID Numbers: Pro00000581, P50CA108786, P30CA014236, SPORE Project 3, CDR0000579683
Study First Received: February 28, 2008
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
adult giant cell glioblastoma
adult gliosarcoma

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

ClinicalTrials.gov processed this record on August 21, 2014