Rituximab and Cladribine in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy such as cladribine work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab with cladribine may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with cladribine works in treating patients with newly-diagnosed mantle cell lymphoma.

Detailed Description
-----------------
OBJECTIVES: Determine whether rituximab and cladribine will increase the complete remission rate and the unconfirmed complete remission rate in patients with mantle cell lymphoma. Determine the time to progression in patients treated with this regimen. Determine the toxic effects of this regimen in these patients. OUTLINE: This is a multicenter study. An initial cohort of 6 patients at Mayo Clinic receives rituximab IV over 4-8 hours on day 1 and cladribine IV over 2 hours on days 4-8. If 2 or more patients experience unacceptable toxicity during the first course, the study is discontinued; otherwise, the study is opened for enrollment at all NCCTG sites. (The phase II study is open for enrollment as of 5/14/04.) Treatment repeats every 28 days for a total of 2-6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

Official Title
-----------------
Phase II Trial of Rituximab and 2-Chlorodeoxyadenosine (2-CDA) in Newly Diagnosed Mantle Cell Lymphoma (MCL)

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: rituximab
* Drug: cladribine


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed mantle cell lymphoma* Measurable or assessable disease defined as at least one of the following: Lymph node or tumor mass that is 2.0 cm or more in at least one dimension by CT scan, MRI, or plain radiograph imaging OR greater than 1.5 cm in at least one dimension by physical exam Splenic enlargement, if the spleen is palpable, at least 3 cm below the left costal margin Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease No known CNS involvement NOTE: *If tumor tissue is unavailable for biopsy, blood or bone marrow specimens may be used to establish patient eligibility provided fusion signals indicate the presence of t(11;14)(q13;q32) by fluorescence in situ hybridization using CCND1/IGH AND mantle cell lymphoma involvement is determined by morphology PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-3 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Total or direct bilirubin no greater than upper limit of normal (ULN) (with or without secondary liver involvement) SGOT no greater than 3 times ULN (5 times ULN if there is liver involvement) Renal Creatinine no greater than 2.0 mg/dL Cardiovascular No myocardial infarction within the past 6 months No uncontrolled high blood pressure No unstable angina No serious uncontrolled cardiac arrhythmia No active congestive heart failure Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after study participation HIV negative No other malignancy within the past 5 years except carcinoma in situ of the cervix, resected basal cell or squamous cell skin cancer, or prostate cancer that is in remission after a radical retropubic prostatectomy or radiotherapy No medical or psychiatric condition that makes the patient a poor risk for this study No active or uncontrolled infection No known hypersensitivity to rituximab or its components or to murine proteins PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy for mantle cell lymphoma Chemotherapy No prior chemotherapy for mantle cell lymphoma Endocrine therapy No prior endocrine therapy for mantle cell lymphoma Radiotherapy No prior radiotherapy Surgery Prior splenectomy allowed (for diagnosis, cytopenia, or symptomatic splenomegaly)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rituximab + cladribine<br>Patients receive rituximab IV over 4-8 hours on day 1 and cladribine IV over 2 hours on days 4-8. If 2 or more patients experience unacceptable toxicity during the first course, the study is discontinued; otherwise, the study is opened for enrollment at all NCCTG sites. Treatment repeats every 28 days for a total of 2-6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years. | Biological: rituximab<br> <br> Drug: cladribine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) and complete remission unconfirmed (CRu) rate at the close of study therapy assessment (after 2, 4, or 6 courses) |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression at any time after therapy |  | Up to 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma