Derivation of Tumor Specific Hybridomas

Vaccination of Patients With Newly Diagnosed Glioblastoma Using Autologous Tumor Lysate and Montanide Emulsion for Derivation of Tumor Specific Hybridomas

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.

Study Overview

• Status: Terminated
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: Tumor Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Autologous Tumor Lysate and Montanide Emulsion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of hybridoma clones that produce anti-glioma antibodies	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Production of Antibodies	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.	6 months
Toxicity of Vaccine	• Determining toxicity of vaccine	6 months
Clone Production Rate	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.	6 months
Lymph Node Biopsy	Determine the safety and toxicity issues related to the Lymph Node Biopsy	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Binding Characteristics	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.	6 months

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: University of Vermont
• Investigators: Principal Investigator: Camilo Fadul, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): May 6, 2015
• Study Completion (ACTUAL): May 6, 2015

Study Registration Dates

• First Submitted: October 3, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (ESTIMATE): October 8, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2018
• Last Update Submitted That Met QC Criteria: April 2, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Immunotherapy, cancer vaccine, glioblastoma, hybridoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Monatide (IMS 3015)
• Other Study ID Numbers: W12209