Rituximab, Methotrexate, Vincristine Sulfate, Procarbazine Hydrochloride, and Cytarabine With or Without Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
Condition: Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Lymphoma; Neurotoxicity; Radiation Toxicity
MeSH terms: Lymphoma; Neurotoxicity Syndromes
Intervention: Rituximab; Cytarabine; Methotrexate; Procarbazine; Vincristine; low-dose whole-brain radiation therapy
Intervention description: One 28-day cycle = 500 mg/m^2 intravenously on day 1 and day 5.; One 28-day cycle = 3 g/m^2 intravenously on day 1 and day 2.; One 28-day cycle = 3.5 g/m^2 intravenously (standard hydration/leucovorin support) on day 2.; One 28-day cycle = 100 mg/m^2 orally on days 2-8.; One 28-day cycle = 1.4 mg/m^2 intravenously, dose capped at 2.4mg, on day 2 and day 16.; Total dose of 2340 cGy administered as 13 daily fractions of 180 cGy over 3 weeks. Participants with progressive disease on magnetic resonance imaging (MRI) do not receive WBRT.
Intervention MeSH terms: Cytarabine; Rituximab; Methotrexate; Vincristine; Procarbazine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: neurotoxicity; chemotherapeutic agent toxicity; radiation toxicity; cognitive/functional effects; primary central nervous system non-Hodgkin lymphoma

Summary:

      RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
      ways. Some find cancer cells and help kill them or carry cancer-killing substances to them.
      Others interfere with the ability of cancer cells to grow and spread. Drugs used in
      chemotherapy, such as methotrexate, vincristine sulfate, procarbazine hydrochloride, and
      cytarabine, work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill
      cancer cells. It is not yet know whether rituximab and combination chemotherapy are more
      effective when given with or without radiation therapy in treating patients with primary
      central nervous system lymphoma.

      PURPOSE: This randomized phase II trial studies how well giving rituximab and combination
      chemotherapy with or without radiation therapy works in treating patients with primary
      central nervous system lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. B-cell non-Hodgkin's lymphoma(NHL) involving the brain, as demonstrated by
             contrast-enhanced Magnetic resonance imaging (MRI) and histologic confirmation by one
             of the following within 6 weeks prior to registration:

               -  A positive cerebral spinal fluid (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

             Note: Patients in whom the type of lymphoma could not be determined or is unknown (eg,
             not enough tissue for further analysis) are assumed to have a B cell lymphoma and are
             eligible.

          2. The patient must agree to submit tissue (i.e., the original H/E stained slides and
             immunohistochemistry studies) for central pathology review post-registration.

          3. No evidence of systemic non-Hodgkin lymphoma as demonstrated by a computed tomography
             (CT) scan of the chest, abdomen and pelvis within 6 weeks prior to registration (Note:
             Bone marrow biopsy is not required for registration but must be obtained prior to
             start of treatment.)

          4. Age ≥ 18

          5. History and physical examination within 6 weeks of registration

          6. Karnofsky performance status (KPS) equal to 50 or higher, with the following exception

             • Patients with KPS 30 to 50 are eligible if the reason for the poor performance
             status is neurologic deficit from primary central nervous system (CNS) lymphoma.
             (Patients with KPS 30 to 50 due to reasons other than primary CNS lymphoma are
             ineligible. Patients with KPS under 30 for any reason are ineligible)

          7. Patient must have documentation of negative HIV-1 testing within 6 weeks prior to
             study registration (Separate counseling and consent as per institutional guidelines)

          8. Complete blood count (CBC)/differential obtained within 2 weeks prior to study
             registration, with adequate bone marrow function defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;

               -  Platelets ≥ 100,000 cells/mm3;

               -  Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention
                  to achieve Hgb ≥ 8.0 g/dl is acceptable.);

          9. Adequate liver function within 2 weeks prior to study registration, defined as
             follows:

               -  Bilirubin < 2.0 mg/dl

               -  Aspartate aminotransferase (AST) <2.5 times upper limit of normal

         10. Adequate renal function within 2 weeks prior to study registration, defined as follows

               -  Serum creatinine < 1.5 mg/dl

               -  Calculated creatinine clearance (CrCl) > 50cc/min/1.73m2, using the
                  Cockcroft-Gault equation, as follows:

             Male: CrCl (ml/min) = (140-age) X (Actual weight in kg) / 72 x serum Creatinine
             (mg/dl).

             Female: CrCl (ml/min) = (140-age) X (Actual weight in kg) X 0.85 / 72 x serum
             Creatinine (mg/dl).

             Note: A measured CrCl from a 24 hour urine collection may also be used.

         11. Women of childbearing potential and male participants must agree to practice adequate
             contraception during therapy

         12. Patient must provide study-specific informed consent prior to study registration

         13. Patient must be able to swallow pills.

        Exclusion Criteria:

          1. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity,
             or cervix are all permissible)

          2. Prior treatment with chemotherapy or radiotherapy for lymphoma or chronic lymphocytic
             leukemia; note that prior chemotherapy for a different cancer is allowable; see
             section 1

          3. Prior cranial irradiation

          4. Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months;

               -  Transmural myocardial infarction within the last 6 months;

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration;

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days before
                  registration

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  Known pre-existing immunodeficiency as seen in organ transplant recipient.

          5. Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic.

          6. Prior allergic reaction to any of the study drugs involved in this protocol.