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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001512
First Posted: November 4, 1999
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose

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.


Condition Intervention Phase
B Cell Lymphoma Follicular Lymphoma Lymphoma Drug: Id-KLH Vaccine Drug: GM-CSF Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 42
Study Start Date: September 9, 1996
Study Completion Date: March 5, 2010
Primary Completion Date: March 5, 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001512


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001512     History of Changes
Obsolete Identifiers: NCT00878488
Other Study ID Numbers: 960133
96-C-0133
First Submitted: November 3, 1999
First Posted: November 4, 1999
Last Update Posted: July 2, 2017
Last Verified: March 5, 2010

Keywords provided by National Institutes of Health Clinical Center (CC):
ProMace Chemotherapy
Indolent Lymphoma
Anti-Idiotype Antibody
GM-CSF
B-Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Vaccines
Immunoglobulins
Antibodies
Immunoglobulin Idiotypes
Immunologic Factors
Physiological Effects of Drugs