Rituximab, Temozolomide, and Methylprednisolone in Treating Patients With Recurrent Primary CNS Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as temozolomide and methylprednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Rituximab may help chemotherapy kill more cancer cells by making cancer cells more sensitive to the drugs. Giving rituximab together with temozolomide and methylprednisolone may be an effective treatment for primary CNS non-Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving rituximab together with temozolomide and methylprednisolone works in treating patients with recurrent primary CNS non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with recurrent primary CNS non-Hodgkin's lymphoma treated with rituximab, temozolomide, and methylprednisolone. Secondary Determine the overall and 6-month progression-free survival of patients treated with this regimen. OUTLINE: Induction therapy: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 and oral temozolomide daily on days 1-7 and 15-21. After day 28, patients with stable disease or better proceed to consolidation therapy. Consolidation therapy: Patients receive oral temozolomide daily on days 1-5. Treatment repeats every 28 days for up to 6 courses. Patients achieving a complete remission proceed to maintenance therapy. Maintenance therapy: Patients receive methylprednisolone IV over 2 hours on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately 13.3 months.

Official Title
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A Phase II Study of Rituximab and Temozolomide in Recurrent Primary CNS Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: methylprednisolone
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary CNS non-Hodgkin's lymphoma by brain biopsy, positive cerebrospinal fluid cytology, or vitrectomy Recurrent disease Measurable disease, define as bi-dimensionally measurable lesions with clearly defined margins by brain MRI or CT scan Radiographical evidence of tumor progression by MRI or CT scan Steroid therapy must be stable for 5 days prior to scan PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy More than 8 weeks Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL (transfusion allowed) Hepatic SGOT < 2 times upper limit of normal (ULN) Bilirubin < 2 times ULN No active or latent hepatitis B infection Renal Creatinine < 1.5 mg/dL OR Creatinine clearance ≥ 60 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No uncontrolled significant medical illness that would preclude study treatment No active infection No active HIV infection No concurrent disease that would dangerously alter drug metabolism or obscure toxicity PRIOR CONCURRENT THERAPY: Biologic therapy At least 7 days since prior interferon or thalidomide No concurrent prophylactic filgrastim (G-CSF) No concurrent immunotherapy Chemotherapy No prior temozolomide At least 14 days since prior methotrexate At least 21 days since prior procarbazine At least 42 days since prior nitrosoureas No other concurrent chemotherapy Endocrine therapy See Disease Characteristics At least 7 days since prior tamoxifen No concurrent hormonal therapy Radiotherapy No concurrent radiotherapy Surgery Not specified Other Recovered from all prior therapy At least 28 days since prior investigational agents At least 28 days since other prior cytotoxic therapy At least 7 days since other prior non-cytotoxic agents (e.g., tretinoin) (radiosenitizers allowed) No other concurrent investigational drugs

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: IV Rituximab<br>IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression | Biological: rituximab<br>* given IV days 1,8, 15 and 22<br>Drug: methylprednisolone<br>* 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)<br>Drug: temozolomide<br>* Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles<br>* Other names: TMZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response | Objective response rate of the combination of Rituximab and TMZ | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Alive at 3 Years | The intent was to measure Median Overall Survival at 3 years, however only one participant was analyzable at this time point. Therefore, the number of participants who survived is reported instead. | 3 years | 
| 1 Year Overall Survival Rate |  | 1 year | 
| 6-month Progression-free Survival | Scan at 6 months Complete response: Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response: Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease: Clinical status and MRI does not qualify for complete response, partial response or progression | 6 months | 

 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