S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

Lymphoma Clinical Trial

Official title:

Pilot Trial of Hyper-CVAD and Methotrexate/ARA C Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00041132
• Other study ID #: CDR0000069445
• Secondary ID: U10CA032102S0213
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2002
• Last updated: October 3, 2012
• Start date: September 2002
• Est. completion date: June 2011

Study information

• Verified date: October 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 2011
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• filgrastim
5 ug/kg
• 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
• cytarabine
12 g/m^2 over days 3-4 of cycles 2,4,6,8
• dexamethasone
40 mg on days 2-5 and 12-15 of cycles 1,3,5,7
• doxorubicin
16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7
• leucovorin
170 mg over days 3-5 of cycles 2,4,6,8
• methotrexate
1000 mg/m^2 over days 2-3 of cycles 2,4,6,8
• vincristine
1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

References & Publications (1)

A multi center trial of hyperCVAD+rituxan in patients with newly diagnosed mantle cell lymphoma EM Epner; J Unger; T Miller; L Rimsza; C Spier; M LeBlanc; R Fisher. Blood 110(11):#387. (2007).

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	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.	assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration	No
Secondary	Response	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.	assessed after cycle 4 and after completion of treatment (168 days)	No
Secondary	Overall Survival	Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause.	assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years	No