S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma | RxWiki

S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

Overview[ - collapse ][ - ]

Purpose	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining rituximab with chemotherapy may kill more cancer cells. PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with rituximab in treating patients who have newly diagnosed mantle cell lymphoma.
Condition	Lymphoma
Intervention	Biological: filgrastim Biological: rituximab Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin Drug: leucovorin Drug: methotrexate Drug: vincristine
Phase	Phase 2
Sponsor	Southwest Oncology Group
Responsible Party	Southwest Oncology Group
ClinicalTrials.gov Identifier	NCT00041132
First Received	July 8, 2002
Last Updated	October 3, 2012
Last verified	October 2012

Tracking Information[ + expand ][ + ]

First Received Date	July 8, 2002
Last Updated Date	October 3, 2012
Start Date	September 2002
Estimated Primary Completion Date	June 2011
Current Primary Outcome Measures	Progression-free Survival [Time Frame: assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration] [Designated as safety issue: No]Progression-Free Survival (PFS) rate at 1 year. PFS measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is a 50% increase in the sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed if a complete response (confirmed, or unconfirmed) was not previously achieved; appearance of a new lesion/site; unequivocal progression of non-measurable disease; or death due to disease without prior documentation of progression.
Current Secondary Outcome Measures	Response [Time Frame: assessed after cycle 4 and after completion of treatment (168 days)] [Designated as safety issue: No]Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of nodes; no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. CRU is complete disappearance of all measurable and non-measurable disease; regressed, non-palpable organs; and one or more exceptions not qualifying for CR (see protocol section 10). PR applies to patients with at least one measurable lesion who do not qualify for CR or CRU. PR is a 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. Overall Survival [Time Frame: assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years] [Designated as safety issue: No]Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause.

Descriptive Information[ + expand ][ + ]

Brief Title	S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma
Official Title	Pilot Trial of Hyper-CVAD and Methotrexate/ARA C Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma
Brief Summary	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining rituximab with chemotherapy may kill more cancer cells. PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with rituximab in treating patients who have newly diagnosed mantle cell lymphoma.
Detailed Description	OBJECTIVES: - Determine the 1-year progression-free survival probability in patients with previously untreated mantle cell lymphoma treated with courses of rituximab and cyclophosphamide, doxorubicin, vincristine, and dexamethasone alternating with courses of rituximab and high-dose cytarabine and methotrexate with leucovorin calcium. - Determine the response rate (complete unconfirmed and complete and partial responses) and survival of patients treated with this regimen. - Determine the toxicity of this regimen in these patients. - Correlate chromosomal breakpoints, translocated immunoglobulin regulatory sequences, and cyclins D1, D2, and D3 with response and progression-free survival in patients treated with this regimen. - Correlate gene expression (measured by DNA microarray analysis) with response and progression-free survival in patients treated with this regimen. OUTLINE: This is a pilot, multicenter study. - Courses 1, 3, 5, and 7: Patients receive rituximab IV on day 1 (courses 1, 3, and 5 only); cyclophosphamide IV over 3 hours twice a day on days 2-4; doxorubicin IV over 24 hours on days 5-7; vincristine IV on days 5 and 12; dexamethasone orally or IV four times a day on days 2-5 and 12-15; and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover. - Courses 2, 4, 6, and 8: Patients receive rituximab IV on day 1 (courses 2, 4, and 6 only); high-dose methotrexate IV over 24 hours on day 2; high-dose cytarabine IV over 2 hours twice a day on days 3-4; oral leucovorin calcium 4 times a day on days 3-10; and G-CSF SC daily beginning on day 5 and continuing until blood counts recover. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for 3 years. Patients with disease progression are followed annually for up to 5 years from study entry. PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Lymphoma
Intervention	Biological: filgrastim 5 ug/kg Other Names: G-CSFBiological: rituximab 375 mg/m^2 on day 1 of cycles 1-6 Drug: cyclophosphamide 300 mg/m^2 on days 2-4 of cycles 1,3,5,7 Other Names: cytoxanDrug: cytarabine 12 g/m^2 over days 3-4 of cycles 2,4,6,8 Other Names: Ara-CDrug: dexamethasone 40 mg on days 2-5 and 12-15 of cycles 1,3,5,7 Drug: doxorubicin 16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7 Other Names: adriamycinDrug: leucovorin 170 mg over days 3-5 of cycles 2,4,6,8 Other Names: leucovorin calciumDrug: methotrexate 1000 mg/m^2 over days 2-3 of cycles 2,4,6,8 Other Names: MTXDrug: vincristine 1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7 Other Names: vincristine sulfate
Study Arm (s)	Experimental: Hyper-CVAD + MTX/Ara-C + Rituximab 21-day cycles of Hyper-CVAD and high-dose methotrexate/cytarabine are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6. Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and filgrastim 5 ug/kg on days 8-21. Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	56
Estimated Completion Date	June 2011
Estimated Primary Completion Date	November 2007
Eligibility Criteria	DISEASE CHARACTERISTICS: - Histologically proven stage III/IV or bulky stage II mantle cell lymphoma of one of the following histologic subtypes: - Nodular - Diffuse - Mantle zone - Blastic - Newly diagnosed and previously untreated disease - Bidimensionally measurable disease PATIENT CHARACTERISTICS: Age: - 18 to 69 Performance status: - Zubrod 0-2 Life expectancy: - Not specified Hematopoietic: - Absolute neutrophil count at least 1,000/mm^3 - Platelet count at least 100,000/mm^3 (50,000/mm^3 if marrow involvement present) Hepatic: - Bilirubin no greater than 1.5 mg/dL (5.0 mg/dL if hepatic involvement present) Renal: - Creatinine no greater than 2.0 mg/dL - Creatinine clearance greater than 50 mL/min Cardiovascular: - Ejection fraction at least 50% by MUGA or 2-D echocardiogram - No significant abnormalities by EKG Other: - Not pregnant or nursing - Fertile patients must use effective contraception - Willing to receive blood product transfusions - No known sensitivity to E. coli-derived proteins - No known AIDS syndrome or HIV-associated complex - No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: - No prior monoclonal antibody therapy Chemotherapy: - No prior chemotherapy for lymphoma Endocrine therapy: - Not specified Radiotherapy: - No prior radiotherapy for lymphoma Surgery: - Not specified
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT00041132
Other Study ID Numbers	CDR0000069445
Has Data Monitoring Committee	No
Information Provided By	Southwest Oncology Group
Study Sponsor	Southwest Oncology Group
Collaborators	National Cancer Institute (NCI)
Investigators	Study Chair: Elliot M. Epner, MD, PhD OHSU Knight Cancer Institute
Verification Date	October 2012