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

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

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Rituximab Vincristine sulfate

U.S. FDA Resources

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:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Rituximab, 375 mg/ m2 IV Day 1, Treatment will be repeated every 21 days.

Cyclophosphamide 750 mg/ m2 IV Day 1, q 21 days

Doxorubicin 50 mg/ m2 IV Day 1, q 21 days

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

Maximum dose of vincristine is 2 mg

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

Locations

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

BJC Foundation

Investigators

Principal Investigator:

Amanda Cashen, MD

Washington University School of Medicine

More Information

Publications:

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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.

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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.

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Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3;403(6769):503-11.

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Montserrat E, López-Guillermo A, Grogan TM, Miller TP, LeBlanc M, Ott G, Kvaloy S, Delabie J, Holte H, Krajci P, Stokke T, Staudt LM; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jun 20;346(25):1937-47.

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.

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Responsible Party:	Washington University School of Medicine ( Amanda Cashen, MD )
Study ID Numbers:	05-0122, 05-0122
Study First Received:	December 28, 2007
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00590941 History of Changes
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:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Hormones
Lymphoma, B-Cell
Anti-Bacterial Agents
Lymphoma, Large-cell
Lymphoma
Alkylating Agents
Immunoglobulins
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders

Antineoplastic Agents, Hormonal
Rituximab
Vincristine
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Doxorubicin
Lymphatic Diseases
Antibodies
B-cell Lymphomas
Tubulin Modulators
Antineoplastic Agents, Alkylating
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Antirheumatic Agents

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Lymphoma, B-Cell
Therapeutic Uses
Lymphoma
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tubulin Modulators

ClinicalTrials.gov processed this record on July 02, 2009