The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma
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.
Timeline
- Start
- 2010-10-14
- Primary completion
- 2017-07-28
- Completion
- 2018-04-18
Outcome
Outcome not reported
Stopped (Enrollment): “The clinical trial was terminated due to poor enrollment”
Publications
- Background Soussain 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.
- Background Sierra 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.
- Background Soussain 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.
- Background Cheng 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.
- Background Abrey 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.
- Background Colombat 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.
- Background Mills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH. BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol. 1995 Mar;13(3):588-95. doi: 10.1200/JCO.1995.13.3.588.
- Background Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. doi: 10.1056/NEJM199512073332305.
- Background Nakasone H, Izutsu K, Wakita S, Yamaguchi H, Muramatsu-Kida M, Usuki K. Autologous stem cell transplantation with PCR-negative graft would be associated with a favorable outcome in core-binding factor acute myeloid leukemia. Biol Blood Marrow Transplant. 2008 Nov;14(11):1262-9. doi: 10.1016/j.bbmt.2008.08.012.
- Background Gondo H, Harada M, Miyamoto T, Takenaka K, Tanimoto K, Mizuno S, Fujisaki T, Nagafuji K, Hayashi S, Eto T, Taniguchi S, Akashi K, Harada N, Yamasaki K, Shibuya T, Matsuishi E, Ohno Y, Makino S, Takamatsu Y, Murakawa M, Teshima T, Hirota Y, Okamura T, Kinukawa N, Niho Y, et al. Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia. Bone Marrow Transplant. 1997 Nov;20(10):821-6. doi: 10.1038/sj.bmt.1700979.
- Background Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
- Background Jeffrey Raizer, DeAngelis Lisa, Andrew Zelenetz et al. Activity of Rituximab in Primary Central Nervous System Lymphoma PCNSL. Proc Am Soc Clin Oncol 19: 2000 (abstr 642)
- Background Rubenstein JL, Fridlyand J, Abrey L, Shen A, Karch J, Wang E, Issa S, Damon L, Prados M, McDermott M, O'Brien J, Haqq C, Shuman M. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007 Apr 10;25(11):1350-6. doi: 10.1200/JCO.2006.09.7311. Epub 2007 Feb 20.
- Background Wong ET, Tishler R, Barron L, Wu JK. Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas. Cancer. 2004 Jul 1;101(1):139-45. doi: 10.1002/cncr.20339.
- Background Enting RH, Demopoulos A, DeAngelis LM, Abrey LE. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology. 2004 Sep 14;63(5):901-3. doi: 10.1212/01.wnl.0000137050.43114.42.
- Background Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
- Background Stupp R, Hegi ME, Gilbert MR, Chakravarti A. Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol. 2007 Sep 10;25(26):4127-36. doi: 10.1200/JCO.2007.11.8554.
- Background Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. doi: 10.1200/JCO.2003.03.036.
- Background Agarwala SS, Kirkwood JM. Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Oncologist. 2000;5(2):144-51. doi: 10.1634/theoncologist.5-2-144.
- Background Agarwala SS, Reyderman L, Statkevich P et al Pharmacokinetic phase I study of temozolomide penetration into CSF in a patient with dural melanoma. Annals of Oncology, supplement 4 to volume 9, 1998, abstract 659 page 138
- Background Vassal G, Tranchand B, Valteau-Couanet D, Mahe C, Couanet D, Schoeppfer C, Grill J, Kalifa C, Hill C, Ardiet C, Hartmann O. Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell transplantation in children with neuroblastoma and medulloblastoma. Bone Marrow Transplant. 2001 Mar;27(5):471-7. doi: 10.1038/sj.bmt.1702806.
- Background Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnston A, Lister TA. Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol. 1983 Sep;1(9):546-51. doi: 10.1200/JCO.1983.1.9.546.
- Background Capizzi RL, Yang JL, Cheng E, Bjornsson T, Sahasrabudhe D, Tan RS, Cheng YC. Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia. J Clin Oncol. 1983 Dec;1(12):763-71. doi: 10.1200/JCO.1983.1.12.763.
- Background Relling MV, Mahmoud HH, Pui CH, Sandlund JT, Rivera GK, Ribeiro RC, Crist WM, Evans WE. Etoposide achieves potentially cytotoxic concentrations in CSF of children with acute lymphoblastic leukemia. J Clin Oncol. 1996 Feb;14(2):399-404. doi: 10.1200/JCO.1996.14.2.399.
- Background Newton HB, Turowski RC, Stroup TJ, McCoy LK. Clinical presentation, diagnosis, and pharmacotherapy of patients with primary brain tumors. Ann Pharmacother. 1999 Jul-Aug;33(7-8):816-32. doi: 10.1345/aph.18353.
- Background Skeel R. Antioneoplastic Drugs and Biologic Response Modifiers: Classification, Use, and Toxicity of Clinically Useful Agents. Pp64-66 in Handbook of Cancer Chemotherapy, 5th edition 1999, Editor Skeel R
- Background Brox LW, Gowans B, Belch A. L-phenylalanine mustard (melphalan) uptake and cross-linking in the RPMI 6410 human lymphoblastoid cell line. Cancer Res. 1980 Apr;40(4):1169-72.
- Background Chabner B. Adduct-Forming Agents: Alkylating Agents and Platinum Analogs. Pp 52-53 in Harrison's Manual of Oncology 2008. Editors Chabner BA, Lynch TJ, Longo DL
- Background Gaspard MH, Maraninchi D, Stoppa AM, Gastaut JA, Michel G, Tubiana N, Blaise D, Novakovitch G, Rossi JF, Weiller PJ, et al. Intensive chemotherapy with high doses of BCNU, etoposide, cytosine arabinoside, and melphalan (BEAM) followed by autologous bone marrow transplantation: toxicity and antitumor activity in 26 patients with poor-risk malignancies. Cancer Chemother Pharmacol. 1988;22(3):256-62. doi: 10.1007/BF00273421.
- Background Hoffmann AL, Buhk JH, Strik H. Neoplastic meningitis from breast cancer: feasibility and activity of long-term intrathecal liposomal Ara-C combined with dose-dense temozolomide. Anticancer Res. 2009 Dec;29(12):5191-5.
- Background Passarin MG, Moretto G, Musso AM, Ottaviani S, Masotto B, Ghimenton C, Iuzzolino P, Buffone E, Ruda R, Soffietti R, Vattemi E, Pedersini R. Intrathecal liposomal cytarabine in combination with temozolomide in low-grade oligoastrocytoma with leptomeningeal dissemination. J Neurooncol. 2010 May;97(3):439-44. doi: 10.1007/s11060-009-0040-0. Epub 2009 Oct 31.
- Background Issa S, Hwang J, Karch J, et al. Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 7595
- Background Prados MD, Yung WK, Fine HA, Greenberg HS, Junck L, Chang SM, Nicholas MK, Robins HI, Mehta MP, Fink KL, Jaeckle KA, Kuhn J, Hess KR, Schold SC Jr; North American Brain Tumor Consortium study. Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study. Neuro Oncol. 2004 Jan;6(1):33-7. doi: 10.1215/S1152851703000309.
- Background Raizer JJ, Malkin MG, Kleber M, Abrey LE. Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy. Neuro Oncol. 2004 Jul;6(3):247-52. doi: 10.1215/S1152851704000122.
- Background Ebert BL, Niemierko E, Shaffer K, Salgia R. Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer. Oncologist. 2003;8(1):69-75. doi: 10.1634/theoncologist.8-1-69.
- Background Korones DN, Benita-Weiss M, Coyle TE, Mechtler L, Bushunow P, Evans B, Reardon DA, Quinn JA, Friedman H. Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Cancer. 2003 Apr 15;97(8):1963-8. doi: 10.1002/cncr.11260.
- Background Rudek MA, Donehower RC, Statkevich P, Batra VK, Cutler DL, Baker SD. Temozolomide in patients with advanced cancer: phase I and pharmacokinetic study. Pharmacotherapy. 2004 Jan;24(1):16-25. doi: 10.1592/phco.24.1.16.34800.
- Background Vera K, Djafari L, Faivre S, Guillamo JS, Djazouli K, Osorio M, Parker F, Cioloca C, Abdulkarim B, Armand JP, Raymond E. Dose-dense regimen of temozolomide given every other week in patients with primary central nervous system tumors. Ann Oncol. 2004 Jan;15(1):161-71. doi: 10.1093/annonc/mdh003.
- Background Dhodapkar M, Rubin J, Reid JM, Burch PA, Pitot HC, Buckner JC, Ames MM, Suman VJ. Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Clin Cancer Res. 1997 Jul;3(7):1093-100.
- Background Handbook of statistics in clinical oncology By John Crowley, Donna Pauler Ankerst Pahse 1 Trials Page 8 Edition 2, 2005
- Background Hahn T, Wolff SN, Czuczman M, Fisher RI, Lazarus HM, Vose J, Warren L, Watt R, McCarthy PL Jr; ASBMT Expert Panel. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidence-based review. Biol Blood Marrow Transplant. 2001;7(6):308-31. doi: 10.1016/s1083-8791(01)80003-3. No abstract available.
- Background Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O'Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F; International Primary CNS Lymphoma Collaborative Group. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol. 2005 Aug 1;23(22):5034-43. doi: 10.1200/JCO.2005.13.524. Epub 2005 Jun 13.
- Background Patel M, McCully C, Godwin K, Balis FM. Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates. J Neurooncol. 2003 Feb;61(3):203-7. doi: 10.1023/a:1022592913323.
- Background Ostermann S, Csajka C, Buclin T, Leyvraz S, Lejeune F, Decosterd LA, Stupp R. Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients. Clin Cancer Res. 2004 Jun 1;10(11):3728-36. doi: 10.1158/1078-0432.CCR-03-0807.
- Background Lowsky et al. Research Protocol for California AML Study.
- Background Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with overdose control. Stat Med. 1998 May 30;17(10):1103-20. doi: 10.1002/(sici)1097-0258(19980530)17:103.0.co;2-9.
- Background Babb JS, Rogatko A. Patient specific dosing in a cancer phase I clinical trial. Stat Med. 2001 Jul 30;20(14):2079-90. doi: 10.1002/sim.848.
- Background Tighiouart M, Rogatko A, Babb JS. Flexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control. Stat Med. 2005 Jul 30;24(14):2183-96. doi: 10.1002/sim.2106.
- Background Zacks s, Rogatko A, Babb J. Optimal Bayesian-feasible dose escalation for cancer phase I trials. Statistics & Probability Letters, 1998, vol. 38, issue 3, pages 215-220
- Background Xu Z, Tighiouart M, Rogatko A. 2007 EWOC 2.0: Interactive Software for Dose Escalation in Cancer Phase I Clinical Trials, Drug Information Journal, 41(2):221-228
- Background Chao ST, Barnett GH, Vogelbaum MA, Angelov L, Weil RJ, Neyman G, Reuther AM, Suh JH. Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy. Cancer. 2008 Oct 15;113(8):2198-204. doi: 10.1002/cncr.23821.
- Background Boiardi A, Silvani A, Pozzi A, Salmaggi A. Radiotherapy at tumor recurrence in primary CNS lymphoma. Neurology. 1998 Jun;50(6):1934-5. doi: 10.1212/wnl.50.6.1934-b. No abstract available.
- Background Plotkin SR, Betensky RA, Hochberg FH, Grossman SA, Lesser GJ, Nabors LB, Chon B, Batchelor TT. Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin Cancer Res. 2004 Sep 1;10(17):5643-6. doi: 10.1158/1078-0432.CCR-04-0159.
- Background Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol. 2008 Jan;86(2):211-5. doi: 10.1007/s11060-007-9464-6. Epub 2007 Sep 21.
- Background Reni M, Mazza E, Foppoli M, Ferreri AJ. Primary central nervous system lymphomas: salvage treatment after failure to high-dose methotrexate. Cancer Lett. 2007 Dec 18;258(2):165-70. doi: 10.1016/j.canlet.2007.10.009. Epub 2007 Nov 13.
- Background Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer. 2007 Mar 26;96(6):864-7. doi: 10.1038/sj.bjc.6603660. Epub 2007 Feb 27.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Temozolomide | Small molecule | 250 mg/m2 | Oral |