Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of two different combination chemotherapy regimens in treating patients who have stage III or stage IV non-Hodgkin's lymphoma.

Detailed Description
-----------------
OBJECTIVES: Compare the overall survival rate, progression free survival rate, clinical and molecular remission rates, and time to treatment failure in patients with newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma treated with chlorambucil, mitoxantrone, and dexamethasone versus fludarabine, mitoxantrone, and dexamethasone. Compare the efficacy and tolerability of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Index score [low risk (score 1) vs intermediate low risk (score 2) vs intermediate high risk (score 3) vs high risk (score 4 or 5)]. Patients are randomized to one of two treatment arms. Arm I: Patients receive mitoxantrone IV on day 1, oral chlorambucil on days 1-10, and oral dexamethasone on days 1-5. Arm II: Patients receive mitoxantrone and dexamethasone as in arm I and fludarabine IV on days 1-3. Treatment continues every 4 weeks for 4-8 courses. Patients are followed at 3, 6, and 12 months, every 6 months for 1 year, and then annually thereafter until clinical relapse. PROJECTED ACCRUAL: A total of 500 patients (250 per arm) will be accrued for this study within 4 years.

Official Title
-----------------
Randomized Trial of MCD Versus FMD in Untreated Advanced Follicular Lymphoma

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

Intervention / Treatment
-----------------
* Drug: chlorambucil
* Drug: dexamethasone
* Drug: fludarabine phosphate
* Drug: mitoxantrone hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically proven newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma REAL classification grade I, II, or III Treatment necessity indicated by presence of the following: B symptoms Bone marrow failure Bulky or progressive disease Compression syndromes No CNS involvement PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: Not specified Life expectancy: Not specified Hematopoietic: No autoimmune hemolytic anemia or active hemolysis Direct Coombs' negative Hepatic: Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN)* Bilirubin no greater than 2.5 times ULN* NOTE: *Unless attributable to lymphoma Renal: Creatinine no greater than 2.5 times ULN (unless attributable to lymphoma) Cardiovascular: No severe cardiac failure Ejection fraction at least 45% Other: Not pregnant or nursing Fertile patients must use effective contraception during and for at least 6 months after study HIV negative No prior malignancy except carcinoma in situ of the cervix or squamous cell skin cancer No other serious medical disease that would limit lifespan or ability to tolerate chemotherapy PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: No concurrent systemic corticosteroids Radiotherapy: Not specified Surgery: Not specified Other: No prior therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: chlorambucil|nan|
|Drug: dexamethasone|nan|
|Drug: fludarabine phosphate|nan|
|Drug: mitoxantrone hydrochloride|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure |  |  | 
| Progression-free survival rate |  |  | 
| Overall survival rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission rate |  |  | 
| Molecular remission rate |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma