Efficacy and Safety Study of Bendamustine With or Without Rituximab in Chronic Lymphoproliferative Disorders

Chronic Lymphocytic Leukaemia Clinical Trial

Official title:

A Retrospective Multicenter Trial on Efficacy and Toxicity of Bendamustine Alone or Associated With Rituximab, As Salvage Therapy in Patients With Chronic Lymphoproliferative Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01832597
• Other study ID #: RetroBENDA
• Status: Completed
• Phase: N/A
• First received: April 8, 2013
• Last updated: April 12, 2013
• Start date: November 2010
• Est. completion date: January 2011

Study information

• Verified date: April 2013
• Source: Gruppo Italiano Studio Linfomi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Observational

Clinical Trial Summary

The purpose of this study is collect and evaluate the clinical experience reached in Italy on the use of bendamustine alone or combined with rituximab as treatment of patients with relapsed or refractory chronic lymphoproliferative disorders.

Description:

All patients who meet the criteria for inclusion will be included in the study. A specific database will be created to collect the following information: personal data, medical history, histology related to the underlying disease, comorbidities, laboratory data, initial staging, data on the dosage and the number of cycles administered, the recorded toxicity data, the clinical response and the main events (relapse, progression, death, and cause of death). These data will then be retrospectively examined in order to obtain information about the life-saving treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with relapsed or refractory chronic lymphoproliferative disorders

• salvage treatment with Bendamustine +/- Rituximab

• age = 18 years

Exclusion Criteria:

• previous treatment with Bendamustine

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukaemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoproliferative Disorders

Locations

Country	Name	City	State
Italy	UO di Ematologia, S.O. Annunziata	Cosenza	CZ
Italy	Dipartimento di Oncologia, Ematologia e Patologie dell'Apparato Respiratorio, Universita` di Modena e Reggio Emilia	Modena	MO
Italy	UO di Ematologia, AOUP Paolo Giaccone,	Palermo	PA

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Studio Linfomi

Country where clinical trial is conducted

Italy, 

References & Publications (26)

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Bergmann MA, Goebeler ME, Herold M, Emmerich B, Wilhelm M, Ruelfs C, Boening L, Hallek MJ; German CLL Study Group. Efficacy of bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase I/II study of the German CLL Study Group. Haematologica. 2005 Oct;90(10):1357-64. — View Citation

Cheson BD, Rummel MJ. Bendamustine: rebirth of an old drug. J Clin Oncol. 2009 Mar 20;27(9):1492-501. doi: 10.1200/JCO.2008.18.7252. Epub 2009 Feb 17. Review. Erratum in: J Clin Oncol. 2009 Jun 10;27(17):2892. — View Citation

Cheson BD, Wendtner CM, Pieper A, Dreyling M, Friedberg J, Hoelzer D, Moreau P, Gribben J, Knop S, Montillo M, Rummel M. Optimal use of bendamustine in chronic lymphocytic leukemia, non-Hodgkin lymphomas, and multiple myeloma: treatment recommendations from an international consensus panel. Clin Lymphoma Myeloma Leuk. 2010 Feb;10(1):21-7. doi: 10.3816/CLML.2010.n.002. Review. — View Citation

Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 Jun 1;111(11):5291-7. doi: 10.1182/blood-2007-12-130120. Epub 2008 Mar 11. — View Citation

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Forconi F, Fabbri A, Lenoci M, Sozzi E, Gozzetti A, Tassi M, Raspadori D, Lauria F. Low-dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic Leukaemia. Hematol Oncol. 2008 Dec;26(4):247-51. doi: 10.1002/hon.868. — View Citation

Giannopoulos K, Dmoszynska A, Kowal M, Wasik-Szczepanek E, Bojarska-Junak A, Rolinski J, Döhner H, Stilgenbauer S, Bullinger L. Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia. Leukemia. 2009 Oct;23(10):1771-8. doi: 10.1038/leu.2009.98. Epub 2009 May 14. — View Citation

Gribben JG. How I treat CLL up front. Blood. 2010 Jan 14;115(2):187-97. doi: 10.1182/blood-2009-08-207126. Epub 2009 Oct 22. Review. — View Citation

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23. Erratum in: Blood. 2008 Dec 15;112(13):5259. — View Citation

Hallek M, Schmitt B, Wilhelm M, Busch R, Kröber A, Fostitsch HP, Sezer O, Herold M, Knauf W, Wendtner CM, Kuse R, Freund M, Franke A, Schriever F, Nerl C, Döhner H, Thiel E, Hiddemann W, Brittinger G, Emmerich B; German Chronic Lymphocytic Leukaemia Study Group. Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group. Br J Haematol. 2001 Aug;114(2):342-8. — View Citation

Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Tremmel L, Merkle K, Montillo M. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009 Sep 10;27(26):4378-84. doi: 10.1200/JCO.2008.20.8389. Epub 2009 Aug 3. — View Citation

Lamanna N, Kalaycio M, Maslak P, Jurcic JG, Heaney M, Brentjens R, Zelenetz AD, Horgan D, Gencarelli A, Panageas KS, Scheinberg DA, Weiss MA. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006 Apr 1;24(10):1575-81. Epub 2006 Mar 6. — View Citation

Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G, Niemeyer CC. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008 Jan 1;14(1):309-17. doi: 10.1158/1078-0432.CCR-07-1061. — View Citation

Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, Blum KA, Flynn JM, Jones JA, Hu W, Moran ME, Mitchell SM, Smith LL, Wagner AJ, Raymond CA, Schaaf LJ, Phelps MA, Villalona-Calero MA, Grever MR, Byrd JC. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009 Dec 10;27(35):6012-8. doi: 10.1200/JCO.2009.22.6944. Epub 2009 Oct 13. — View Citation

Lissitchkov T, Arnaudov G, Peytchev D, Merkle Kh. Phase-I/II study to evaluate dose limiting toxicity, maximum tolerated dose, and tolerability of bendamustine HCl in pre-treated patients with B-chronic lymphocytic leukaemia (Binet stages B and C) requiring therapy. J Cancer Res Clin Oncol. 2006 Feb;132(2):99-104. Epub 2005 Nov 15. — View Citation

Mössner E, Brünker P, Moser S, Püntener U, Schmidt C, Herter S, Grau R, Gerdes C, Nopora A, van Puijenbroek E, Ferrara C, Sondermann P, Jäger C, Strein P, Fertig G, Friess T, Schüll C, Bauer S, Dal Porto J, Del Nagro C, Dabbagh K, Dyer MJ, Poppema S, Klein C, Umaña P. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010 Jun 3;115(22):4393-402. doi: 10.1182/blood-2009-06-225979. Epub 2010 Mar 1. — View Citation

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Oskolkova OV, Afonyushkin T, Leitner A, von Schlieffen E, Gargalovic PS, Lusis AJ, Binder BR, Bochkov VN. ATF4-dependent transcription is a key mechanism in VEGF up-regulation by oxidized phospholipids: critical role of oxidized sn-2 residues in activation of unfolded protein response. Blood. 2008 Jul 15;112(2):330-9. doi: 10.1182/blood-2007-09-112870. Epub 2008 May 1. — View Citation

Robak T, Dmoszynska A, Solal-Céligny P, Warzocha K, Loscertales J, Catalano J, Afanasiev BV, Larratt L, Geisler CH, Montillo M, Zyuzgin I, Ganly PS, Dartigeas C, Rosta A, Maurer J, Mendila M, Saville MW, Valente N, Wenger MK, Moiseev SI. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1756-65. doi: 10.1200/JCO.2009.26.4556. Epub 2010 Mar 1. — View Citation

Tageja N, Nagi J. Bendamustine: something old, something new. Cancer Chemother Pharmacol. 2010 Aug;66(3):413-23. doi: 10.1007/s00280-010-1317-x. Epub 2010 Apr 8. Review. — View Citation

Wierda W, O'Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, Do KA, Cortes J, Koller C, Beran M, Ferrajoli A, Giles F, Lerner S, Albitar M, Kantarjian H, Keating M. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4070-8. Epub 2005 Mar 14. — View Citation

Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1749-55. doi: 10.1200/JCO.2009.25.3187. Epub 2010 Mar 1. Erratum in: J Clin Oncol. 2010 Aug 1;28(22):3670. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Evaluate the activity of Bendamustine +/- Rituximab in term of ORR	At least 2 months after completion of therapy	No
Secondary	Progression Free Survival (PFS) and Overall Survival (OS)	Evaluate the activity of Bendamustine +/- Rituximab in term of PFS and OS	From the date of frist treatment cycle until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 150 months	No
Secondary	Number of Adverse Events	Assess to efficacy of Bendamustine +/- Rituximab in term of grade III and IV National Cancer Institute Common Toxicity Criteria (NCI CTC) adverse events	From the date of first tratment cycle until 6 months after the date of last treatment cycle	Yes