Biology of Blood and Marrow Transplantation
Volume 16, Issue 8 , Pages 1145-1154 , August 2010

Phase I/II Trial of GN-BVC, a Gemcitabine and Vinorelbine-Containing Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Recurrent and Refractory Hodgkin Lymphoma

  • Sally Arai

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • Corresponding Author InformationCorrespondence and reprint requests: Sally Arai, MD, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305.
    • ,
  • Renee Letsinger

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Ruby M. Wong

      Affiliations

    • Department of Health Research and Policy, Division of Biostatistics, Stanford University Medical Center, Stanford, California
    • ,
  • Laura J. Johnston

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Ginna G. Laport

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Robert Lowsky

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • David B. Miklos

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Judith A. Shizuru

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Wen-Kai Weng

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Philip W. Lavori

      Affiliations

    • Department of Health Research and Policy, Division of Biostatistics, Stanford University Medical Center, Stanford, California
    • ,
  • Karl G. Blume

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Robert S. Negrin

      Affiliations

    • Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California
    • ,
  • Sandra J. Horning

      Affiliations

    • Division of Medical Oncology, Stanford University Medical Center, Stanford, California

Received 31 January 2010 ,Accepted 22 February 2010.

References 

  1. Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomized trial. Lancet. 1993;341:1051–1054
  2. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomized trial. Lancet. 2002;359:2065–2071
  3. Velasquez WS, Cabanillas F, Salvador P, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988;71:117–122
  4. Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol. 2002;13:1628–1635
  5. Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001;97:616–623
  6. Baetz T, Belch A, Couban S, et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 2003;14:1762–1767
  7. Bartlett NL, Niedzwiecki D, Johnson JL, et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007;18:1071–1079
  8. Josting A, Rudolph C, Mapara M, et al. Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Ann Oncol. 2005;16:116–123
  9. Glossmann J-P, Josting A, Pfistner B, Paulus U, Engert A. A randomized trial of chemotherapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) plus peripheral stem cell transplantation (PBSCT) vs single-agent high-dose chemotherapy followed by BEAM plus PBSCT in patients with relapsed Hodgkin's disease (HD-R2). Ann Hematol. 2002;81:424–429
  10. Reece DE, Barnett MJ, Connors JM, et al. Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol. 1991;9:1871–1879
  11. Nademanee A, O'Donnell MR, Snyder DS, et al. High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. Blood. 1995;85:1381–1390
  12. Horning SJ, Chao NJ, Negrin RS, et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood. 1997;89:801–813
  13. Wheeler C, Eickhoff C, Elias A, et al. High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant. 1997;3:98–106
  14. Frankovich J, Donaldson SS, Lee Y, et al. High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic lung injury syndromes. Biol Blood Marrow Transplant. 2001;7:49–57
  15. Stiff PJ, Unger JM, Forman SJ, et al. The value of augmented preparative regimens combined with an autologous bone marrow transplant for the management of relapsed or refractory Hodgkin disease: a Southwest Oncology Group phase II trial. Biol Blood Marrow Transplant. 2003;9:529–539
  16. Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, Horning SJ. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood. 1997;89:814–822
  17. Cao TM, Negrin RS, Stockerl-Goldstein KE, et al. Pulmonary toxicity syndrome in breast cancer patients undergoing BCNU-containing high-dose chemotherapy and autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2000;6:387–394
  18. Reece DE, Nevell TJ, Sayegh A, et al. Regimen-related toxicity and non-relapse mortality with high-dose cyclophosphamide, carmustine (BCNU) and etoposide (VP16-213) (CBV) and CBV plus cisplatin (CBVP) followed by autologous stem cell transplantation in patients with Hodgkin's disease. Bone Marrow Transplant. 1999;23:1131–1138
  19. Stuart MJ, Chao NS, Horning SJ, et al. Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease. Biol Blood Marrow Transplant. 2001;7:552–560
  20. Benekli M, Smiley SL, Younis T, et al. Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hemtopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma. Bone Marrow Transplant. 2008;41:613–619
  21. Takvorian T, Parker LM, Hochberg FH, Canellos GP. Autologous bone-marrow transplantation: host effects of high-dose BCNU. J Clin Oncol. 1983;1:610–620
  22. Wheeler C, Antin JH, Churchill WH, et al. Cyclophosphamide, carmustine, etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. J Clin Oncol. 1990;8:648–656
  23. Kalaycioglu M, Kavuru M, Tauson L, Bolwell B. Empiric prednisone therapy for pulmonary toxic reaction after high-dose chemotherapy containing carumustine (BCNU). Chest. 1995;107:482–487
  24. Horwitz SM, Negrin RS, Blume KG, et al. Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood. 2004;103:777–783
  25. Jagannath S, Dicke KA, Armitage JO, et al. High-dose cyclophosphamide, carmustine, and etoposide and autologous bone marrow transplantation for relapsed Hodgkin's disease. Ann Intern Med. 1986;104:163–168
  26. Borchmann P, Schnell R, Diehl V, Engert A. New drugs in the treatment of Hodgkin's disease. Ann Oncol. 1998;9(Suppl 5):S103–S108
  27. Santoro A, Bredenfeld H, Devizzi L, et al. Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol. 2000;18:2615–2619
  28. Zinzani PL, Bendandi M, Stefoni V, et al. Value of gemcitabine treatment in heavily pretreated Hodgkin's disease patients. Haematologica. 2000;85:926–929
  29. Lucas JB, Horwitz SM, Horning SJ, Sayegh A. Gemcitabine is active in relapsed Hodgkin's disease. J Clin Oncol. 1999;17:2627–2628
  30. Devizzi L, Santoro A, Bonfanti V, Viviani S, Bonadonna G. Vinorelbine: a new promising drug in Hodgkin's disease. Leukemia Lymphoma. 1996;22:409–414
  31. Bonfante V, Viviani S, Santoro A, et al. Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease. Br J Haematol. 1998;103:533–535
  32. Rule S, Tighe M, Davies S, Johnson S. Vinorelbine in the treatment of lymphoma. Hematol Oncol. 1998;16:101–105
  33. Grunewald R, Kantarjian H, Du M, et al. Gemcitabine in leukemia: a phase I clinical, plasma, and cellular pharmacology study. J Clin Oncol. 1992;10:406–413
  34. Mani S, Kugler JW, Knost JA, et al. Phase II trial of 150-minute weekly infusion of gemcitabine in advanced colorectal cancer: minimal activity in colorectal cancer. Invest New Drugs. 1998;16:275–278
  35. Brand R, Capadano M, Tempero M. A phase I trial of weekly gemcitabine administered as a prolonged infusion in patients with pancreatic cancer and other solid tumors. Invest New Drugs. 1997;15:331–341
  36. Hainsworth JD, Burris HA, Litchy S, et al. Gemcitabine and vinorelbine in the second-line treatment of non-small cell lung carcinoma patients: a Minnie Pearl Cancer Research Network phase II trial. Cancer. 2000;88:1353–1358
  37. Lorusso V, Carpagnano F, Frasci G, et al. Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small cell lung cancer. J Clin Oncol. 2000;18:405–411
  38. Delord JP, Raymond E, Chaouche M, et al. A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies. Ann Oncol. 2000;11:73–79
  39. DeLeve LD, Shulman HM, McDonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis. 2002;22:27–42
  40. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–586
  41. Hutchings M, Mikhaeel NG, Fields PA, Nunan T, Timothy AR. Prognostic value of interim FDG-PET after two or 3 cycles of chemotherapy in Hodgkin lymphoma. Ann Oncol. 2005;16:1160–1168
  42. Gallamini A, Hutchings M, Rigacci L, et al. Early interim2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from the Joint Italian-Danish Study. J Clin Oncol. 2007;25:3746–3752
  43. Poen JC, Hoppe RT, Horning SJ. High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: the impact of involved field radiotherapy on patterns of failure and survival. Int J Radiat Oncol Biol Phys. 1996;36:3–12
  44. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stati Assoc. 1958;53:457–481
  45. Horning SJ. Primary refractory Hodgkin's disease. Ann Oncol. 1998;9(Suppl 5):S97–S101
  46. Lavoie JC, Connors JM, Phillips GL, et al. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood. 2005;106:1473–1478
  47. Moskowitz AJ, Perales MA, Kewalramani T, et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol. 2009;146:158–163
  48. Cheng YC, Rondon G, Yang Y, et al. The use of high-dose cyclophosphamide, carmustine, and thiotepa plus autologous hematopoietic stem cell transplantation as consolidation therapy for high-risk primary breast cancer after primary surgery or neoadjuvant chemotherapy. Biol Blood Marrow Transplant. 2004;10:794–804
  49. Wadhwa PD, Fu P, Koc ON, et al. High-dose carmustine, etoposide, and cisplatin for autologous stem cell transplantation with or without involved-field radiation for relapsed/refractory lymphoma: an effective regimen with low morbidity and mortality. Biol Blood Marrow Transplant. 2005;11:13–22
  50. Chien JW, Madtes DK, Clark JG. Pulmonary function testing prior to hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;35:429–435
  51. Josting A, Franklin J, May M, et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2002;20:221–230
  52. Majhail NS, Weisdorf DJ, Defor TE, et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma. Biol Blood Marrow Transplant. 2006;12:1065–1072
  53. Nademanee A, Molina A, Fung H, et al. High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission. Biol Blood Marrow Transplant. 1999;5:292–298
  54. Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer. 2007;109:2481–2489
  55. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol. 2009;145:369–372
  56. Moskowitz CH, Nimer SD, Zelenetz AD, et al. Normalization of FDG-PET Pre-ASCT with additional non-cross resistant chemotherapy improves EFS in patients with relapsed and primary refractory Hodgkin lymphoma-Memorial Sloan Kettering Protocol 04-047. Blood. 2008;112:(abstr 775)
  57. Morschhauser F, Brice P, Ferme C, et al. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM Study Group. J Clin Oncol. 2008;26:5980–5987
  58. Bartlett N, Forero-Torres A, Rosenblatt J, et al. Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). J Clin Oncol. 2009;27:15s(Suppl) (abstr 8500)
  59. Younes A, Fanale M, Pro B, et al. A phase II study of a novel oral isotype-selective histone deacetylase (HDAC) inhibitor in patients with relapsed or refractory Hodgkin lymphoma. J Clin Oncol. 2007;25:18s(Suppl) (abstr 8000)
  60. Fehniger TA, Larson S, Trinkaus K, et al. A phase II multicenter study of lenalidomide in patients with relapsed or refractory classical Hodgkin lymphoma: preliminary results. Blood. 2008;112:(abstr 2595)
  61. Mendler JH, Friedberg JW. Salvage therapy in Hodgkin's lymphoma. Oncologist. 2009;14:425–432

 Financial disclosure: See Acknowledgments on page 1152.

PII: S1083-8791(10)00095-9

doi: 10.1016/j.bbmt.2010.02.022

Biology of Blood and Marrow Transplantation
Volume 16, Issue 8 , Pages 1145-1154 , August 2010

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