Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's cancer proteins may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may make a stronger immune response and kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving vaccine therapy together with GM-CSF works in treating patients with CNS lymphoma.

Detailed Description
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OBJECTIVES: Primary To determine the proportion of patients with CNS lymphoma who develop anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) humoral immune responses in the serum and/or CSF following patient-specific immunotherapy comprising recombinant tumor-derived immunoglobulin Id-KLH conjugate vaccine and sargramostim (GM-CSF). To assess the safety and tolerability of this regimen in these patients. Secondary To evaluate the progression-free survival (PFS) of patients treated with this regimen. To determine the time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine. To assess the correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival. Tertiary To evaluate the kinetics of humoral immune response development in patients treated with this regimen. OUTLINE: Pre-immunotherapy: Patients submit a tumor sample for manufacturing of the idiotype (Id)-keyhole limpet hemocyanin (KLH) conjugate vaccine and undergo placement of an Ommaya reservoir. Patients then receive induction therapy comprising methotrexate IV once every 2 weeks until a maximum radiographic response is achieved, as assessed by MRI of the brain. Patients then receive methotrexate IV once a month for 6 months. Patients with leptomeningeal or CSF involvement also receive intraventricular thiotepa twice a week until the CSF is clear on three evaluations and then once a week until the CSF is clear on four evaluations. Patients under 55 years of age also undergo whole brain radiotherapy (or craniospinal radiotherapy when extensive leptomeningeal disease is present). Patients who achieve a stable response to induction therapy proceed to immunotherapy. Immunotherapy: Patients receive recombinant tumor-derived immunoglobulin Id-KLH conjugate vaccine subcutaneously (SC) on day 1 of weeks 0, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76. Patients also receive sargramostim (GM-CSF) SC on days 1-4 of the same weeks as the Id-KLH conjugate vaccine. After completion of therapy, patients are followed periodically for up to 2 years.

Official Title
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A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of Patient-Specific Immunotherapy, Recombinant Idiotype Conjugated to KLH (Id-KLH) and Administered With GM-CSF, in Patients With CNS Lymphoma

Conditions
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Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer

Intervention / Treatment
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* Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine
* Biological: sargramostim
* Drug: methotrexate
* Drug: thiotepa
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or CSF cytologically confirmed CNS lymphoma with any of the following clinical histories: Primary CNS lymphoma at initial diagnosis Primary CNS lymphoma at relapse Systemic lymphoma with CNS disease at initial diagnosis or at relapse Adequate fresh tissue or cell pellet available for analysis by Genitope Corporation to determine adequacy for idiotype (Id) manufacturing Tumor must express both functional light and heavy chain genes No tumors known or found to be surface immunoglobulin negative Not in leukemic phase (i.e., > 5,000/mm³ circulating tumor cells) PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100% WBC ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ Hemoglobin ≥ 10 g/dL Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's disease) Creatinine ≤ 1.5 times ULN Able to undergo placement of an Ommaya reservoir Able to receive induction therapy (chemotherapy with or without brain radiotherapy) with intent to induce remission Speaks English or Spanish No other malignancy within the past 3 years, except adequately treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ Not pregnant or nursing No immunosuppressive viral infections as evidenced by HIV antibody or antigen, hepatitis B antigen, or hepatitis C antibody or antigen positivity No history of autoimmune disease that required treatment within the past 5 years, including previously treated autoimmune hemolytic anemia or immune thrombocytopenia PRIOR CONCURRENT THERAPY: More than 30 days since prior and no concurrent participation in another therapeutic clinical trial More than 2 weeks since prior steroids No concurrent immunosuppressives, including corticosteroids Transient use of optical or nasal steroid solutions is allowed No other concurrent anticancer therapy or therapy for non-Hodgkin lymphoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: methotrexate IV once every 2 weeks<br> | Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine<br> <br> Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: thiotepa<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) immune response rate in the CSF |  |  | 
| Safety and tolerability |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  |  | 
| Time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine |  |  | 
| Correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival |  |  | 
| Kinetics of humoral immune response development |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary central nervous system non-Hodgkin lymphoma, primary central nervous system Hodgkin lymphoma, stage IV adult T-cell leukemia/lymphoma, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, stage IV mycosis fungoides/Sezary syndrome, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, intraocular lymphoma, post-transplant lymphoproliferative disorder, cutaneous B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, small intestine lymphoma