Rituximab, Methotrexate, Procarbazine and Vincristine Followed by High-dose Chemotherapy With Autologous Stem-cell Rescue in Newly-diagnosed Primary CNS Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of this new treatment offered in this study. PCNSL can be cured in less than half of patients with standard treatment, a combination of chemotherapy and brain radiation. Also, the combination of chemotherapy and brain radiation may result in serious lasting side effects. Most patients older than age 60 develop memory problems, difficulty walking or inability to control their bladder. Some patients younger than age 60 also develop these side effects.

Official Title
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Rituximab, Methotrexate, Procarbazine and Vincristine Followed by High-dose Chemotherapy With Autologous Stem-cell Rescue in Newly-diagnosed Primary CNS Lymphoma (PCNSL)

Conditions
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CNS Lymphoma, CNS Brain Cancer, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Other: Rituximab, Methotrexate, Vincristine, Procarbazine, PBPCs collection, Busulfan, Thiotepa, and Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have non-Hodgkin's lymphoma involving the brain, as demonstrated by CT or MRI and histologic confirmation by one of the following: A positive CSF cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers. A biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma. Brain biopsy. Patients must be HIV-1 negative. Patient must have left ventricular ejection fraction ≥ 50%. Patients must have no evidence of systemic lymphoma. This must be demonstrated by a CT scan of the chest, abdomen and pelvis prior to registration. Patients must have adequate bone marrow function (defined as peripheral leucocyte count >3000 cells/mm3 and platelet count > 100,000 cells/mm3), liver function (bilirubin < 2.0 mg%), and adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance > 50cc/min/1.73M2). Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment. Patients must be between 18 and 72 years-old. Patients must sign an informed consent. Exclusion Criteria: Prior cranial irradiation Other active primary malignancy with the exception of basal cell carcinoma of the skin and cervical carcinoma in situ. Pre-existing immunodeficiency such as renal transplant recipient. Prior treatment with chemotherapy for CNS lymphoma.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 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: 1<br>Rituximab, methotrexate (MTX), procarbazine and vincristine (R-MPV). The peripheral blood stem cell (PBSC) harvest procedure will be performed at the discretion of the hematology attending (usually after the 1st or 2nd cycle of R-MPV)and high dose chemotherapy Busulfan, Thiotepa, and Cyclophosphamide. Patients will be off study at the time of death. All patients will be followed for survival every 6 months throughout their lifetime. Survival status may be obtained by phone call, clinical visit or medical records (e.g. physician notes/laboratory results of clinic or hospital visit. | Other: Rituximab, Methotrexate, Vincristine, Procarbazine, PBPCs collection, Busulfan, Thiotepa, and Cyclophosphamide<br>* The initial treatment will consist of cycles of 14 days. Each cycle will start with rituximab, which will be given by vein on day 1. On day 2 you will be admitted to the hospital and will receive 3 other drugs: Methotrexate will be given by vein over 2 to 3 hours only on day 2. Vincristine will be given as a single injection over a few minutes only on day 2. Procarbazine is a pill that you will take at bedtime for 7 nights starting on day 2. Procarbazine is only given every other cycle.<br>* Other names: by vein. You will be in the hospital for at least 3 weeks.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate the safety and efficacy of the use of R-MPV followed by high-dose chemotherapy using thiotepa, cyclophosphamide and busulfan with stem cell rescue in patients with newly diagnosed PCSNL. |  | 1-year event-free survival and acute treatment-related toxicity. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate response rates with the combination of rituximab and MPV as induction chemotherapy. |  | after 5 cycles |