The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma

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.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

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

• BACKGROUNDSoussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. doi: 10.1200/JCO.2007.13.5533. Epub 2008 Apr 14. PMID 18413641
• BACKGROUNDSierra del Rio M, Rousseau A, Soussain C, Ricard D, Hoang-Xuan K. Primary CNS lymphoma in immunocompetent patients. Oncologist. 2009 May;14(5):526-39. doi: 10.1634/theoncologist.2008-0236. Epub 2009 May 11. PMID 19433528
• BACKGROUNDSoussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. doi: 10.1200/JCO.2001.19.3.742. PMID 11157026
• BACKGROUNDCheng T, Forsyth P, Chaudhry A, Morris D, Gluck S, Russell JA, Stewart DA. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant. 2003 Apr;31(8):679-85. doi: 10.1038/sj.bmt.1703917. PMID 12692608
• BACKGROUNDAbrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. doi: 10.1200/JCO.2003.05.024. PMID 14615443
• BACKGROUNDColombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broet S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. doi: 10.1038/sj.bmt.1705452.