Derivation of Tumor Specific Hybridomas

This study has suspended participant recruitment.
(Pending amendment approval through local IRB)
Sponsor:
Collaborator:
University of Vermont
Information provided by (Responsible Party):
Camilo Fadul, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01702792
First received: October 3, 2012
Last updated: December 14, 2013
Last verified: December 2013
  Purpose

This is a non-randomized, open-label study in patients with newly diagnosed glioblastoma to determine the ability to generate human hybridomas from lymph nodes draining an autologous tumor vaccine injection and demonstrate that the hybridomas secrete glioblastoma-specific antibodies.


Condition Intervention Phase
Glioblastoma
Biological: Tumor Vaccine
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vaccination of Patients With Newly Diagnosed Glioblastoma Using Autologous Tumor Lysate and Montanide Emulsion for Derivation of Tumor Specific Hybridomas

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • number of hybridoma clones that produce anti-glioma antibodies [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The primary technical endpoint demonstrating the feasibility of the pilot study will be based upon the total count of the number of generated hybridoma clones sourced from the dermal vaccine draining lymph nodes that are determined to be producing anti-glioma antibodies.


Secondary Outcome Measures:
  • Production of Antibodies [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    Secondary outcomes will include:

    Determining how many hybridoma clones produce glioblastoma-specific antibodies. The initial secondary endpoint will include the counting of the number of hybridoma clones sourced from the dermal vaccine draining lymph nodes that generate specific glioma antibodies.


  • Toxicity of Vaccine [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    • Determining toxicity of vaccine

  • Clone Production Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Determining whether B cells sourced from the vaccine nodes produce more anti-tumor antibody hybridomas than the non-vaccine node. The rate of producing these clones will be compared according to the source of the B cells. Thus, B cells recovered from vaccine related nodes will be compared to B cells recovered from the non-vaccine node.

  • Lymph Node Biopsy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Determine the safety and toxicity issues related to the Lymph Node Biopsy


Other Outcome Measures:
  • Tumor Binding Characteristics [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    Exploratory objectives will include:

    • Determining the rate of tumor binding antibodies from hybridomas derived from circulating B cells.
    • Determining the tumor-binding profile of antibodies present in the blood.


Estimated Enrollment: 5
Study Start Date: January 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tumor Vaccine
1 x 107 TCE tumor lysate in 0.5 ml Lactated Ringers Solution (approximately 1 mg of tumor lysate protein) and equivalent volume of adjuvant will be injected 2 weeks and 3 weeks (2 vaccinations) after surgery in the intradermal skin of the upper thigh. There will be 2 vaccine administrations and patients will be followed for 2 months after inguinal node removal for any possible vaccine/study-related toxicity.
Biological: Tumor Vaccine
Tumor cells obtained at the time of surgery are irradiated with 10,000 Gy and freeze fractured. Lysate at 1x107 tumor cell equivalent (TCE) will be used for vaccination with adjuvant, Montanide ISA 51 VG.
Other Name: Autologous Tumor Lysate and Montanide Emulsion

Detailed Description:

The intradermal vaccine will be injected 20cm in the anterior thigh. Vaccination will be done twice and separated by one week. The first vaccination will be performed approximately 2 weeks after surgery.

Approximately one week after the second vaccination one or two vaccine-draining lymph node(s) will be removed. The lymph node(s) will be identified using SN technology. One or two lymph node(s) will be removed.

Lymph nodes will be processed for recovery of B cells and formation of hybridomas.

  Eligibility

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

Inclusion Criteria:

  • Patients with confirmed new diagnosis of glioblastoma and who have a yield of at least 8x10(7) tumor cells obtained at the time of surgery
  • Age > 18 years
  • KPS Score of greater than or equal to 70
  • Adequate bone marrow as evidenced by:

Absolute lymphocyte count > 1,000/uL Platelet count > 50,000/uL

  • Adequate renal function as evidenced by serum creatinine < 2.0
  • Patients must be able to read, understand and provide informed consent to participate in the trial.
  • Patients of childbearing potential must agree to use an effective form of contraception during the study and for 90 days following vaccination (an effective form of contraception is an oral contraceptive or a double barrier method)

Exclusion Criteria:

A patient may not be enrolled in the trial if any of the following criteria are met:

  • Patients receiving dexamethasone > 8 mg/day during the week before vaccination.
  • Patients who are pregnant or lactating
  • Patients with active second malignancy.
  • Any other medical conditions, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
  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: NCT01702792

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, Vermont
University of Vermont - Vermont Cancer Center
Burlington, Vermont, United States, 05405
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
University of Vermont
Investigators
Principal Investigator: Camilo Fadul, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided

Responsible Party: Camilo Fadul, Director, Neuro-Oncology Program, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01702792     History of Changes
Other Study ID Numbers: W12209
Study First Received: October 3, 2012
Last Updated: December 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
Immunotherapy, cancer vaccine, glioblastoma, hybridoma

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 18, 2014