Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT00639639 | Completed Phase 1 DMC

• 4 other identifiers: Pro00003877CDR0000589624DUMC-8108-07-1R1Discretionary Funds
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vaccines may help the body build an effective immune response to kill cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy together with radiation therapy and chemotherapy may kill more cancer cells. PURPOSE: This randomized phase I/II trial is studying how well vaccine therapy works in treating patients with newly diagnosed glioblastoma multiforme recovering from lymphopenia caused by temozolomide.

Conditions

Malignant Neoplasms of Brain

Keywords

adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Feasibility and safety of vaccination with cytomegalovirus pp65-LAMP mRNA-loaded dendritic cells (DCs) with or without autologous lymphocyte transfer

  26 months

Secondary Outcomes (6)

• Humoral and cellular immune responses

  26 months

• Time to progression

  From time of surgery/diagnosis to date of progression.

• Differential ability of indium In-111-labeled DCs to track to the inguinal lymph nodes under different skin preparative conditions

  At vaccine # 4

• Differential ability of indium In-111-labeled DCs to track to lymph nodes on the tumor bearing and non-tumor bearing side of the cervical lymph nodes

  At vaccine # 4

• Immunologic cell infiltrate in recurrent tumors

  At progression

Study Arms (4)

Arm I (first randomization)

EXPERIMENTAL

Patients receive CMV-ALT IV over 45-90 minutes (course 1 only) and CMV pp65-LAMP mRNA-loaded DC (CMV-DC) vaccine intradermally and administered in equal portions to each inguinal region. Vaccination repeats every 1-3 weeks for up to 3 doses in the absence of unacceptable toxicity.

Biological: therapeutic autologous dendritic cells; Biological: therapeutic autologous lymphocytes

Arm II (first randomization)

EXPERIMENTAL

Patients receive CMV-DC vaccine intradermally and administered in equal portions to each inguinal region. Vaccination repeats every 1-3 weeks for up to 3 doses in the absence of unacceptable toxicity.

Biological: therapeutic autologous dendritic cells

Arm I (second randomization)

EXPERIMENTAL

Within 6 to 24 hours prior to vaccination, patients undergo skin site preparation with unpulsed DCs at the vaccination site in one inguinal region. Patients then receive indium In 111-labeled CMV-DC.

Biological: therapeutic autologous dendritic cells

Arm II (second randomization)

EXPERIMENTAL

Within 6 to 24 hours prior to vaccination, patients undergo vaccination skin site preparation in the opposite inguinal region with tetanus toxoid. Patients then receive 111 In-labeled CMV-DC.

Biological: tetanus toxoid; Biological: therapeutic autologous dendritic cells

Interventions

tetanus toxoid BIOLOGICAL

Given by injection

Arm II (second randomization)

therapeutic autologous dendritic cells BIOLOGICAL

Given intradermally

Arm I (first randomization); Arm I (second randomization); Arm II (first randomization); Arm II (second randomization)

therapeutic autologous lymphocytes BIOLOGICAL

Given IV

Arm I (first randomization)

Eligibility Criteria

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

You may qualify if:

• Age \>18 years of age.
• World Health Organization (WHO) Grade IV glioma with definitive resection prior to leukapheresis with residual radiographic contrast enhancement on most recent CT or MRI of \<1 cm in maximal diameter in any axial plane.
• Karnofsky Performance Status (KPS ) of \> 80% and a Curran Group status of I-IV.

You may not qualify if:

• Radiographic or cytologic evidence of leptomeningeal or multicentric disease at the time of enrollment.
• Prior conventional anti-tumor therapy other than steroids, RT, Avastin or TMZ.
• Pregnant or need to breast feed during the study period (Negative Beta-Human Chorionic Gonadotrophin \[HCG\] test required).
• Requirement for continuous corticosteroids above physiologic levels at time of first vaccination.
• Active infection requiring treatment or an unexplained febrile (\> 101.5o F) illness.
• Known immunosuppressive disease or human immunodeficiency virus infection.
• Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease.
• Allergic or unable to tolerate TMZ for reasons other than lymphopenia.
• Patients with previous inguinal lymph node dissection.

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 (2)

• Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366-9. doi: 10.1038/nature14320. Epub 2015 Mar 11.

  PMID: 25762141 RESULT

• Batich KA, Reap EA, Archer GE, Sanchez-Perez L, Nair SK, Schmittling RJ, Norberg P, Xie W, Herndon JE 2nd, Healy P, McLendon RE, Friedman AH, Friedman HS, Bigner D, Vlahovic G, Mitchell DA, Sampson JH. Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination. Clin Cancer Res. 2017 Apr 15;23(8):1898-1909. doi: 10.1158/1078-0432.CCR-16-2057.

  PMID: 28411277 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Tetanus Toxoid

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Katherine Peters, MD, PhD

  Duke Univeristy Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• 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: March 19, 2008
• First Posted: March 20, 2008
• Study Start: February 6, 2006
• Primary Completion: April 15, 2017
• Study Completion: June 1, 2022
• Last Updated: March 13, 2023

Record last verified: 2023-03

Locations

US (1)