Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines

June 30, 2017 updated by: National Cancer Institute (NCI)

The idiotype of the immunoglobulin on a given B cell malignancy (Id) can serve as a clonal marker, and a previous pilot study in lymphoma patients has demonstrated that autologous Id protein can be formulated into an immunogenic, tumor specific antigen by conjugation to a carrier protein (KLH) and administration with an emulsion-based adjuvant. The goals of vaccine development in the current study are to develop vaccines: 1) with improved potency and 2) which are more effective at inducing cell-mediated immune responses. The selection of GM-CSF as the immunological "adjuvant" is a direct extension of our laboratory studies in small animal models demonstrating that GM-CSF can enhance the potency of the prototype Id-KLH vaccine by augmenting almost exclusively the cellular arm of the immune response.

The objectives of this study are: 1) to evaluate cellular and humoral immune responses against the unique idiotype of the patient's lymphoma and 2) to evaluate the ability of the Id vaccine to clear the bone marrow of malignant cells detectable by pathologic examination or molecular examination (polymerase chain reaction amplification of the rearranged bcl-2 oncogene).

The goal of this study is to treat previously untreated patients with follicular lymphomas to complete remission or minimal residual disease with ProMACE chemotherapy. Three to six months after completion of chemotherapy, in an effort to reduce the relapse rate (by eradicating microscopic disease resistant to chemotherapy), patients will receive an autologous Id vaccine administered in combination with GM-CSF. Id-KLH (0.5 mg) is administered subcutaneously. GM-CSF is administered subcutaneously locally with the vaccine on the day of vaccination and for the three consecutive days following vaccination as close to the initial vaccination site as possible at one of two doses (patients are randomized to either a high or low dose, 500 or 100 micrograms/m2).

We plan to accrue 42 patients. Twenty-nine patients have been enrolled. Sixteen patients have entered and/or completed the vaccination phase. Patients have demonstrated significant lymphoproliferative responses specific for autologous idiotype of a magnitude which is significantly greater than previously observed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The idiotype of the immunoglobulin on a given B cell malignancy (Id) can serve as a clonal marker, and a previous pilot study in lymphoma patients has demonstrated that autologous Id protein can be formulated into an immunogenic, tumor specific antigen by conjugation to a carrier protein (KLH) and administration with an emulsion-based adjuvant. The goals of vaccine development in the current study are to develop vaccines: 1) with improved potency and 2) which are more effective at inducing cell-mediated immune responses. The selection of GM-CSF as the immunological "adjuvant" is a direct extension of our laboratory studies in small animal models demonstrating that GM-CSF can enhance the potency of the prototype Id-KLH vaccine by augmenting almost exclusively the cellular arm of the immune response.

The objectives of this study are: 1) to evaluate cellular and humoral immune responses against the unique idiotype of the patient's lymphoma and 2) to evaluate the ability of the Id vaccine to clear the bone marrow of malignant cells detectable by pathologic examination or molecular examination (polymerase chain reaction amplification of the rearranged bcl-2 oncogene).

The goal of this study is to treat previously untreated patients with follicular lymphomas to complete remission or minimal residual disease with ProMACE chemotherapy. Three to six months after completion of chemotherapy, in an effort to reduce the relapse rate (by eradicating microscopic disease resistant to chemotherapy), patients will receive an autologous Id vaccine administered in combination with GM-CSF. Id-KLH (0.5 mg) is administered subcutaneously. GM-CSF is administered subcutaneously locally with the vaccine on the day of vaccination and for the three consecutive days following vaccination as close to the initial vaccination site as possible at one of two doses.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 must meet all of the following eligibility criteria.

Tissue diagnosis of: follicular small cleaved cell, or follicular mixed lymphoma with surface IgM, IgG or IgA phenotype with a monoclonal heavy and light chain. Pathology slides must be submitted to the NIH Pathology Department for review.

Stage III or IV lymphoma.

Only previously untreated patients are eligible.

Previous treatment with radiation alone (less than TBI) is permissible.

A single peripheral lymph node of at least 2 cm size accessible for biopsy/harvest.

Karnofsky status greater than or equal to 70 percent.

Life expectancy of greater than 1 year.

Serum creatinine less than or equal to 1.5 mg per dl unless felt to be secondary to lymphoma.

Bilirubin less than or equal to 1.5 mg/dl unless felt to be secondary to lymphoma or Gilbert's disease. SGOT/SGPT less than or equal to 3.5 times upper limit of normal.

Ability to give informed consent. Ability to return to clinic for adequate follow-up for the period that the protocol requires.

EXCLUSION CRITERIA:

Prior total body irradiation.

Presence of antibodies to HIV, hepatitis B surface antigen or other active infectious process.

Pregnancy or lactation. Fertile men and women must plan to use effective contraception. A beta-HCG level will be obtained in women of child-bearing potential.

Patients with previous or concomitant malignancy, regardless of site, except curatively treated squamous or basal cell carcinoma of the skin, or effectively treated carcinoma in situ of the cervix.

Patients unwilling to give informed consent.

Failure to meet any of the inclusion criteria.

Any medical or psychiatric condition that in the opinion of the protocol chairman would compromise the patient's ability to tolerate this treatment will be excluded from this protocol.

Patient with CNS lymphoma (current or previously treated) will not be eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 9, 1996

Primary Completion (Actual)

March 5, 2010

Study Completion (Actual)

March 5, 2010

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

November 3, 1999

First Posted (Estimate)

November 4, 1999

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

March 5, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 960133
  • 96-C-0133

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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