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

NCT ID: NCT00001512

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-09-09
• Study Completion Date: 2010-03-05

Brief Summary

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.

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.

Conditions

B Cell Lymphoma; Follicular Lymphoma; Lymphoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Id-KLH Vaccine

Intervention Type: DRUG

GM-CSF

Intervention Type: DRUG

Eligibility 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.

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Stevenson GT, Stevenson FK. Antibody to a molecularly-defined antigen confined to a tumour cell surface. Nature. 1975 Apr 24;254(5502):714-6. doi: 10.1038/254714a0. No abstract available.

Reference Type: BACKGROUND

PMID: 47617 (View on PubMed)

Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517-22. doi: 10.1056/NEJM198203043060906. No abstract available.

Reference Type: BACKGROUND

PMID: 6173751 (View on PubMed)

Daley MJ, Gebel HM, Lynch RG. Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy. J Immunol. 1978 May;120(5):1620-4.

Reference Type: BACKGROUND

PMID: 77876 (View on PubMed)

Other Identifiers

96-C-0133

Identifier Type: -

Identifier Source: secondary_id

960133

Identifier Type: -

Identifier Source: org_study_id

NCT00878488

Identifier Type: -

Identifier Source: nct_alias