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Genetic Determinations for Side Effects and Response Rate for Patients Receiving Chemotherapy With Diffuse Large Cell Lymphoma

This study is currently recruiting participants.
Verified by Washington University School of Medicine, November 2007

Sponsors and Collaborators: Washington University School of Medicine
BJC Foundation
Information provided by: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00590941
  Purpose

The purpose of this study is to determine whether people have genes that make them more likely to respond to chemotherapy and/or have side effects from chemotherapy for diffuse large cell lymphoma.


Condition Intervention
Lymphoma
Diffuse Large Cell
Genetic: Blood draw
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone

MedlinePlus related topics:   Lymphoma  

ChemIDplus related topics:   Doxorubicin   Doxorubicin hydrochloride   Cyclophosphamide   Prednisone   Vincristine   Rituximab   Globulin, Immune   Immunoglobulins   Vincristine sulfate  

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Other, Randomized, Open Label, Single Group Assignment, Efficacy Study
Official Title:   Candidate Gene Polymorphisms and Response to Rituximab-CHOP in Patients With Diffuse Large Cell Lymphoma

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Negative [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan after 2 cycles of R-CHOP [ Time Frame: 2 cycles of R-CHOP ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response after six cycles of R-CHOP [ Time Frame: 6 Cycles of R-CHOP ] [ Designated as safety issue: No ]
  • progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Grade 3-4 toxicity [ Time Frame: 6 cycles of R-CHOP ] [ Designated as safety issue: Yes ]

Estimated Enrollment:   50
Study Start Date:   February 2005
Estimated Study Completion Date:   February 2007

Intervention Details:
    Genetic: Blood draw
    Patients will have a blood sample collected for genotyping of the FCGR3A gene (immunoglobulin Fc G receptor IIIa), the ABCB1 gene (ATP Binding Cassette Beta 1; also called MDR1), and other candidate genes. Patients will be treated with R-CHOP for six cycles, which is standard therapy for advanced stage DLCL. Response will be monitored by an FDG-PET scan performed after 2 cycles of R-CHOP and restaging exams performed upon completion of chemotherapy. Gene polymorphisms will be analyzed to establish which polymorphisms predict response to R-CHOP.
    Drug: Rituximab
    Rituximab, 375 mg/ m2 IV Day 1, Treatment will be repeated every 21 days.
    Drug: Cyclophosphamide
    Cyclophosphamide 750 mg/ m2 IV Day 1, q 21 days
    Drug: Doxorubicin
    Doxorubicin 50 mg/ m2 IV Day 1, q 21 days
    Drug: Vincristine

    Vincristine* 1.4 mg/ m2 IV Day 1, q 21 days

    *Maximum dose of vincristine is 2 mg

    Drug: Prednisone
    Prednisone 100 mg PO Days 1-5, q 21 days
Detailed Description:

Upon enrollment in the study, patients will have a blood sample collected for genotyping of the FCGR3A gene (immunoglobulin Fc G receptor IIIa), the ABCB1 gene (ATP Binding Cassette Beta 1; also called MDR1), and other candidate genes. Patients will be treated with R-CHOP for six cycles, which is standard therapy for advanced stage DLCL. Response will be monitored by an FDG-PET scan performed after 2 cycles of R-CHOP and restaging exams performed upon completion of chemotherapy. Gene polymorphisms will be analyzed to establish which polymorphisms predict response to R-CHOP.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  • Histologically proven diffuse large B-cell non-Hodgkin's lymphoma according to the WHO classification, with measurable or evaluable disease
  • No prior therapy for NHL. Patient may be enrolled in this study after the first cycle of R-CHOP if all screening evaluations were performed prior to the first cycle of chemotherapy.
  • Ann Arbor stage 3 or 4
  • Age greater than or equal to 18 years
  • Patient must give written informed consent.
  • A patient enrolled in another clinical trial may also enroll in this study if the other trial has an R-CHOP treatment arm and the patient is randomized to the R-CHOP only arm. Registration to this study must occur after randomization in the other trial.

Exclusion Criteria:

  • CNS involvement
  • Known HIV positive
  • T-cell lymphoma or history of indolent NHL
  • Patients who will be treated with radiation therapy
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590941

Contacts
Contact: Amanda Cashen, MD     314-362-3515     acashen@im.wustl.edu    
Contact: Leslie Foster, MHA, BS     314-362-8547     fosterl@ccadmin.wustl.edu    

Locations
United States, Missouri
Washington University School of Medicine     Recruiting
      St. Louis, Missouri, United States, 63110
      Contact: Leslie Foster, MHA, BS     314-362-8547     fosterl@ccadmin.wustl.edu    
      Contact: Jenny Edrington     314-362-0202     edringtj@ccadmin.wustl.edu    
      Principal Investigator: Amanda Cashen, MD            
      Sub-Investigator: Nancy Bartlett, MD            
      Sub-Investigator: Farrokh Dehdashti, MD            
      Sub-Investigator: Barry Siegel, MD            

Sponsors and Collaborators
Washington University School of Medicine
BJC Foundation

Investigators
Principal Investigator:     Amanda Cashen, MD     Washington University School of Medicine    
  More Information

Publications:
[No authors listed] A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun 1;89(11):3909-18.
 
McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93.
 
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6.
 
Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, Lowe A, Kunkel LA, Fisher RI. Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97.
 
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.
 
Elstrom R, Guan L, Baker G, Nakhoda K, Vergilio JA, Zhuang H, Pitsilos S, Bagg A, Downs L, Mehrotra A, Kim S, Alavi A, Schuster SJ. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood. 2003 May 15;101(10):3875-6. Epub 2003 Jan 16.
 
Lavely WC, Delbeke D, Greer JP, Morgan DS, Byrne DW, Price RR, Hallahan DE. FDG PET in the follow-up management of patients with newly diagnosed Hodgkin and non-Hodgkin lymphoma after first-line chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Oct 1;57(2):307-15.
 
Zinzani PL, Magagnoli M, Chierichetti F, Zompatori M, Garraffa G, Bendandi M, Gherlinzoni F, Cellini C, Stefoni V, Ferlin G, Tura S. The role of positron emission tomography (PET) in the management of lymphoma patients. Ann Oncol. 1999 Oct;10(10):1181-4.
 
Mikhaeel NG, Timothy AR, O'Doherty MJ, Hain S, Maisey MN. 18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin's Lymphoma-comparison with CT. Leuk Lymphoma. 2000 Nov;39(5-6):543-53.
 
Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G. Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Sep;13(9):1356-63.
 
Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood. 1999 Jul 15;94(2):429-33.
 
Römer W, Hanauske AR, Ziegler S, Thödtmann R, Weber W, Fuchs C, Enne W, Herz M, Nerl C, Garbrecht M, Schwaiger M. Positron emission tomography in non-Hodgkin's lymphoma: assessment of chemotherapy with fluorodeoxyglucose. Blood. 1998 Jun 15;91(12):4464-71.
 
Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med. 2002 Aug;43(8):1018-27.
 
Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G. Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Sep;13(9):1356-63.
 
Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G. Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma. Haematologica. 2000 Jun;85(6):613-8.
 
Vitolo U, Botto B, Capello D, Vivenza D, Zagonel V, Gloghini A, Novero D, Parvis G, Calvi R, Ariatti C, Milan I, Bertini M, Boccomini C, Freilone R, Pregno P, Orsucci L, Palestro G, Saglio G, Carbone A, Gallo E, Gaidano G. Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma. Leukemia. 2002 Feb;16(2):268-75.
 
Houldsworth J, Olshen AB, Cattoretti G, Donnelly GB, Teruya-Feldstein J, Qin J, Palanisamy N, Shen Y, Dyomina K, Petlakh M, Pan Q, Zelenetz AD, Dalla-Favera R, Chaganti RS. Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. Blood. 2004 Mar 1;103(5):1862-8. Epub 2003 Nov 13.
 
Hermine O, Haioun C, Lepage E, d'Agay MF, Briere J, Lavignac C, Fillet G, Salles G, Marolleau JP, Diebold J, Reyas F, Gaulard P. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 1996 Jan 1;87(1):265-72.
 

Responsible Party:   Washington University School of Medicine ( Amanda Cashen, MD )
Study ID Numbers:   05-0122, 05-0122
First Received:   December 28, 2007
Last Updated:   December 28, 2007
ClinicalTrials.gov Identifier:   NCT00590941
Health Authority:   United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Lymphoma  
Rituximab  
CHOP  

Study placed in the following topic categories:
Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Vincristine
Cyclophosphamide
Doxorubicin
Lymphoma, B-Cell
Lymphoma, large-cell
Lymphatic Diseases
B-cell lymphomas
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Hemic and Lymphatic Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Hormonal
Mitosis Modulators
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms

ClinicalTrials.gov processed this record on May 08, 2008