S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: dexamethasone

Drug: methotrexate

Drug: doxorubicin

Drug: leucovorin

Drug: cyclophosphamide

Biological: filgrastim

Drug: cytarabine

Biological: rituximab

Drug: vincristine

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00041132

S0213 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

CDR0000069445

Details and patient eligibility

About

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.

Full 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.

Enrollment

56 patients

Sex

All

Ages

18 to 69 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

56 participants in 1 patient group

Hyper-CVAD + MTX/Ara-C + Rituximab

Experimental group

Description:

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.

Treatment: