Clinical trial NCT00041132: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage III mantle cell lymphoma
stage IV mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival
timeFrame: assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration
Secondary outcomes:
measure: Response
timeFrame: assessed after cycle 4 and after completion of treatment (168 days)
measure: Overall Survival
timeFrame: assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years
Other outcomes:
Locations:
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Elliot M. Epner, MD, PhD
role: STUDY_CHAIR
References:
citation: 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).