Rituximab+mVPDL for CD20(+) Adult Acute Lymphoblastic Leukemia

Summary

The investigators would like to propose a phase-2 prospective multicenter trial evaluating the efficacy of rituximab combination with our current chemotherapy strategy for adult Acute Lymphoblastic Leukemia (ALL), in order to prove out whether the addition of rituximab during induction, consolidation, and post-alloHCT status can improve the outcome in terms of relapse-free survival (RFS) when compared with our prior data as a historical control.

Timeline

Start

2011-11

Primary completion

2018-01-01

Completion

2019-01-01

Publications

• Background Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003 Mar 1;21(5):774-80. doi: 10.1200/JCO.2003.02.053. Epub 2003 Mar 1.
• Background Hallbook H, Gustafsson G, Smedmyr B, Soderhall S, Heyman M; Swedish Adult Acute Lymphocytic Leukemia Group; Swedish Childhood Leukemia Group. Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006 Oct 1;107(7):1551-61. doi: 10.1002/cncr.22189.
• Background Todeschini G, Tecchio C, Meneghini V, Pizzolo G, Veneri D, Zanotti R, Ricetti MM, Solero P, April F, Perona G. Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin. Leukemia. 1998 Feb;12(2):144-9. doi: 10.1038/sj.leu.2400912.
• Background Thomas D, O'Brien S, Faderl S, Ravandi F, Jabbour E, Pierce S, Cortes J, Kantarjian H. Anthracycline dose intensification in adult acute lymphoblastic leukemia: lack of benefit in the context of the fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen. Cancer. 2010 Oct 1;116(19):4580-9. doi: 10.1002/cncr.25319.
• Background Tomblyn MB, Arora M, Baker KS, Blazar BR, Brunstein CG, Burns LJ, DeFor TE, Dusenbery KE, Kaufman DS, Kersey JH, MacMillan ML, McGlave PB, Miller JS, Orchard PJ, Slungaard A, Tomblyn MR, Vercellotti GM, Verneris MR, Wagner JE, Weisdorf DJ. Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. J Clin Oncol. 2009 Aug 1;27(22):3634-41. doi: 10.1200/JCO.2008.20.2960. Epub 2009 Jul 6.
• Background Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
• Background Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. doi: 10.1182/blood-2007-10-116582. Epub 2007 Nov 29.
• Background Pituch-Noworolska A, Hajto B, Mazur B, Sonta-Jakimczyk D, Balwierz W, Janota-Krawczyk E, Kowalska H, Malinowska I, Modzelewska M, Wasik M. Expression of CD20 on acute lymphoblastic leukemia cells in children. Neoplasma. 2001;48(3):182-7.
• Background Maury S, Huguet F, Leguay T, Lacombe F, Maynadie M, Girard S, de Labarthe A, Kuhlein E, Raffoux E, Thomas X, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Rousselot P, Macintyre E, Ifrah N, Dombret H, Bene MC; Group for Research on Adult Acute Lymphoblastic Leukemia. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica. 2010 Feb;95(2):324-8. doi: 10.3324/haematol.2009.010306. Epub 2009 Sep 22.
• Background Borowitz MJ, Shuster J, Carroll AJ, Nash M, Look AT, Camitta B, Mahoney D, Lauer SJ, Pullen DJ. Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study. Blood. 1997 Jun 1;89(11):3960-6.
• Background Jeha S, Behm F, Pei D, Sandlund JT, Ribeiro RC, Razzouk BI, Rubnitz JE, Hijiya N, Howard SC, Cheng C, Pui CH. Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2006 Nov 15;108(10):3302-4. doi: 10.1182/blood-2006-04-016709. Epub 2006 Aug 8.
• Background Thomas DA, O'Brien S, Jorgensen JL, Cortes J, Faderl S, Garcia-Manero G, Verstovsek S, Koller C, Pierce S, Huh Y, Wierda W, Keating MJ, Kantarjian HM. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood. 2009 Jun 18;113(25):6330-7. doi: 10.1182/blood-2008-04-151860. Epub 2008 Aug 14.
• Background Al Gwaiz LA, Bassioni W. Immunophenotyping of acute lymphoblastic leukemia using immunohistochemistry in bone marrow biopsy specimens. Histol Histopathol. 2008 Oct;23(10):1223-8. doi: 10.14670/HH-23.1223.
• Background Claviez A, Eckert C, Seeger K, Schrauder A, Schrappe M, Henze G, von Stackelberg A. Rituximab plus chemotherapy in children with relapsed or refractory CD20-positive B-cell precursor acute lymphoblastic leukemia. Haematologica. 2006 Feb;91(2):272-3.
• Background Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. doi: 10.1002/cncr.21776.
• Background Thomas DA, O'Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Ravandi F, Verstovsek S, Jorgensen JL, Bueso-Ramos C, Andreeff M, Pierce S, Garris R, Keating MJ, Cortes J, Kantarjian HM. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010 Aug 20;28(24):3880-9. doi: 10.1200/JCO.2009.26.9456. Epub 2010 Jul 26.
• 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 Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.
• Background Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wormann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trumper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. doi: 10.1182/blood-2005-01-0016. Epub 2005 Aug 25.
• Background Griffin TC, Weitzman S, Weinstein H, Chang M, Cairo M, Hutchison R, Shiramizu B, Wiley J, Woods D, Barnich M, Gross TG; Children's Oncology Group. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Feb;52(2):177-81. doi: 10.1002/pbc.21753.
• Background Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grunhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jager U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Buhler A, Winkler D, Zenz T, Bottcher S, Ritgen M, Mendila M, Kneba M, Dohner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2;376(9747):1164-74. doi: 10.1016/S0140-6736(10)61381-5.
• Background Ratanatharathorn V, Pavletic S, Uberti JP. Clinical applications of rituximab in allogeneic stem cell transplantation: anti-tumor and immunomodulatory effects. Cancer Treat Rev. 2009 Dec;35(8):653-61. doi: 10.1016/j.ctrv.2009.07.004. Epub 2009 Aug 13.
• Background Dworzak MN, Schumich A, Printz D, Potschger U, Husak Z, Attarbaschi A, Basso G, Gaipa G, Ratei R, Mann G, Gadner H. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008 Nov 15;112(10):3982-8. doi: 10.1182/blood-2008-06-164129. Epub 2008 Sep 9.
• Background Stanciu-Herrera C, Morgan C, Herrera L. Anti-CD19 and anti-CD22 monoclonal antibodies increase the effectiveness of chemotherapy in Pre-B acute lymphoblastic leukemia cell lines. Leuk Res. 2008 Apr;32(4):625-32. doi: 10.1016/j.leukres.2007.07.002. Epub 2007 Aug 15.
• Background Gaipa G, Basso G, Maglia O, Leoni V, Faini A, Cazzaniga G, Bugarin C, Veltroni M, Michelotto B, Ratei R, Coliva T, Valsecchi MG, Biondi A, Dworzak MN; I-BFM-ALL-FCM-MRD Study Group. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia. 2005 Jan;19(1):49-56. doi: 10.1038/sj.leu.2403559.
• Background Gokbuget N, Hoelzer D. Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. Ann Hematol. 2004 Apr;83(4):201-5. doi: 10.1007/s00277-003-0752-8. Epub 2003 Nov 26.
• Background Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
• Background Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.
• Background Mohty M, Marchetti N, El-Cheikh J, Faucher C, Furst S, Blaise D. Rituximab as salvage therapy for refractory chronic GVHD. Bone Marrow Transplant. 2008 May;41(10):909-11. doi: 10.1038/bmt.2008.12. Epub 2008 Feb 18. No abstract available.
• Background Okamoto M, Okano A, Akamatsu S, Ashihara E, Inaba T, Takenaka H, Katoh N, Kishimoto S, Shimazaki C. Rituximab is effective for steroid-refractory sclerodermatous chronic graft-versus-host disease. Leukemia. 2006 Jan;20(1):172-3. doi: 10.1038/sj.leu.2403996. No abstract available.
• Background Zaja F, Bacigalupo A, Patriarca F, Stanzani M, Van Lint MT, Fili C, Scime R, Milone G, Falda M, Vener C, Laszlo D, Alessandrino PE, Narni F, Sica S, Olivieri A, Sperotto A, Bosi A, Bonifazi F, Fanin R; GITMO (Gruppo Italiano Trapianto Midollo Osseo). Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant. 2007 Aug;40(3):273-7. doi: 10.1038/sj.bmt.1705725. Epub 2007 Jun 4.
• Background Kebriaei P, Saliba RM, Ma C, Ippoliti C, Couriel DR, de Lima M, Giralt S, Qazilbash MH, Gajewski JL, Ha CS, Champlin RE, Khouri IF. Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia. Bone Marrow Transplant. 2006 Aug;38(3):203-9. doi: 10.1038/sj.bmt.1705425. Epub 2006 Jun 26.
• Baek DW, Park HS, Sohn SK, Kim DY, Kim I, Ahn JS, Do YR, Lee SR, Eom HS, Lee WS, Kim SH, Lee HS, Lee YJ, Moon JH, Lee JH; Adult Acute Lymphoblastic Leukemia Working Party, the Korean Society of Hematology. Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study. Korean J Intern Med. 2023 Sep;38(5):734-746. doi: 10.3904/kjim.2022.401. Epub 2023 Jun 20.

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Indications