Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma
Condition: Primary Central Nervous System Lymphoma
MeSH terms: Lymphoma
Intervention: Rituximab plus Temozolomide
Intervention description: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Intervention MeSH terms: Rituximab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; CNS; rituximab; temozolomide

Summary:

      This study will evaluate the safety and efficacy of high-dose rituximab combined with
      temozolomide in the treatment of patients with Primary Central Nervous System Lymphomas
      (PCNSL). This novel combination will be evaluated in PCNSL patients who are 60 years of age
      or older, or in patients 18 years or older who refuse methotrexate-based treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed CD20 positive primary B-cell CNS lymphoma (PCNSL) confirmed
             by one of the following:

               -  Brain biopsy or resection;

               -  Cerebrospinal fluid (CSF) cytology for lymphoma or monoclonal lymphocyte
                  population as defined by cell surface markers.

          2. No evidence of systemic non-Hodgkin's lymphoma.

          3. Male or female, and:

               -  60 years of age or older, or

               -  18 years of age or older and decline methotrexate-based treatment.

          4. Measurable contrast-enhancing disease by MRI of brain and or spine (with gadolinium
             contrast).

          5. ECOG PS equals 2 or less.

          6. No more than 2 prior chemotherapy regimens.

          7. Adequate hematologic, renal, and hepatic function.

          8. Ability to swallow oral medications.

          9. Female patients who are not of childbearing potential, and female patients of
             childbearing potential who agree to use adequate contraceptive measures, who are not
             breastfeeding, and who have a negative serum pregnancy test within 72 hours prior to
             start of treatment.

         10. Male patients willing to use adequate contraceptive measures.

         11. Life expectancy 8 weeks or greater.

         12. HIV negative.

         13. Archival tumor block (or 20 unstained slides) for biomarker testing. Patients without
             archived tumor block material will be allowed to participate in the study.

         14. Willingness and ability to comply with study and followup procedures.

         15. Ability to understand the nature of this study and give written informed consent.

         16. Bone marrow biopsy must be negative for lymphoma.

        Exclusion Criteria:

          1. Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.

          2. Prior bone marrow or organ transplantation.

          3. Chemotherapy or investigational drug therapy for cancer up to 21 days prior to day-1
             of study.

          4. T-cell primary CNS lymphoma.

          5. Known hypersensitivity to dacarbazine (DTIC).

          6. Active, clinically serious infection greater than CTCAE grade 2. Patients may be
             eligible upon resolution of the infection.

          7. Positive test results for chronic hepatitis BsAg infection.

          8. Chronic treatment with steroids or other immunosuppressive agents for medical
             conditions other than cancer. Patients who require steroids for treatment of
             tumor-associated cerebral edema are eligible.

          9. History of other malignancy up to 5 years prior to study entry which could affect
             compliance with the protocol or interpretation of results. History of curatively
             treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the
             cervix, low grade, early stage, localized prostate cancer treated surgically with
             curative intent, ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy
             alone with curative intent, are generally eligible.

         10. History of unstable or newly diagnosed angina pectoris, recent myocardial infarction
             (within 6 months of enrollment), New York Heart Association Classification III or IV.

         11. Vaccination with a live-virus vaccine up to 4 weeks prior to onset of study treatment.

         12. Impairment of gastrointestinal (GI) function or GI disease that, in the opinion of the
             investigator, may significantly alter the absorption of study drug (e.g., Crohn's
             disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption
             syndrome).

         13. Significant, concurrent, uncontrolled medical condition which, in the opinion of the
             investigator, may interfere with patient participation in the study.

         14. Pregnant or lactating female.