The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma
Condition: B-Cell Lymphoma Originating in the CNS
MeSH terms: Lymphoma; Lymphoma, B-Cell
Intervention: Temozolomide
Intervention description: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m2 (cumulative total dose of 1250 mg/m2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; Primary Central Nervous System B-cell Lymphoma; Autologous Stem Cell Transplant; Temozolomide; B-Cell Lymphoma; RBEAM; Conditioning Regimen

Summary:

      The primary purpose of the study will be testing the dosing of temozolomide to find the
      target dose that a person can tolerate. The other part of the study will be determining how
      helpful it can be to CNS lymphoma patients by adding temozolomide to the "conditioning
      regimen" prior to stem cell transplantation.

      This research study is designed to test the investigational use of temozolomide as part of a
      conditioning regimen prior to stem cell transplantation. This drug has not yet been approved
      by the U.S. Food and Drug Administration (FDA) to be used in the setting of stem cell
      transplantation in lymphomas of the brain (central nervous system or CNS) but it has been
      studied and used before in transplantation with reasonable results.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients ≥ 18 years of age and ≤ 75 years of age

          2. Patients must have Central Nervous System (CNS) involvement with a mature B-cell
             non-Hodgkin's Lymphoma, (WHO criteria)

          3. Patients must meet one of the below criteria:

               -  Patients who have achieved a complete response (CR) or partial response (PR)
                  after initial therapy for Central Nervous System (CNS) B-cell lymphoma, OR

               -  Patients with relapsed or progressed disease following therapy for CNS B-cell
                  lymphoma who has achieved a subsequent CR or PR following salvage chemotherapy,
                  OR

               -  Patients who are initially refractory to therapy for CNS B-cell lymphoma but who
                  have achieved a CR or PR following a salvage chemotherapy regimen, OR

               -  Patients who have developed CNS relapse from systemic B-cell Non-Hodgkin's
                  lymphoma, and have evidence of chemotherapy sensitive lymphoma.

          4. Patients fit for autologous stem cell transplantation

          5. Patients able to understand and willing to sign a written informed consent document

        Exclusion Criteria:

          1. Patients whose life expectancy is severely limited by diseases other than malignancy

          2. Karnofsky Performance Score <60

          3. Patients who are pregnant or breastfeeding

          4. Patients who are HIV seropositive

          5. Patients who have an uncontrolled infection (presumed or documented) with progression
             after appropriate therapy for greater than one month

          6. Patients with symptomatic coronary artery disease, uncontrolled congestive heart
             failure. Left Ventricular Ejection Fraction is not required to be measured, however if
             it is measured, patient is excluded if ejection fraction is <30%

          7. Patients requiring supplementary continuous oxygen. DLCO is not required to be
             measured, however if it is measured, patient is excluded if DLCO <35%.

          8. Patients with clinical or laboratory evidence of liver disease will be evaluated for
             the cause of liver disease, its clinical severity in terms of liver function and
             histology, and for the degree of portal hypertension. Patients with any of the
             following liver function abnormalities will be excluded

               1. Fulminant liver failure

               2. Cirrhosis with evidence of portal hypertension or bridging fibrosis

               3. Alcoholic hepatitis

               4. Esophageal varices

               5. A history of bleeding esophageal varices

               6. Hepatic encephalopathy

               7. Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the
                  prothrombin time

               8. Ascites related to portal hypertension

               9. Chronic viral hepatitis with total serum bilirubin >3 mg/dL

              10. Symptomatic biliary disease

          9. Patients with non-B-cell lymphomas or brain tumors that are not lymphomas are Excluded
             from the study. Non-B-cell lymphomas include: any T-cell lymphoma, natural killer
             (NK)-cell lymphomas, and Hodgkin lymphomas

         10. Patients for whom an insufficient number of stem cells (<2 X 106/kg) have been
             collected