Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines
| Status: | Completed |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | September 1996 |
| End Date: | March 2010 |
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.
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.
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.
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.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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