Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Gemcitabine in Treating Patients With Previously Untreated Aggressive Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and gemcitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with gemcitabine to see how well it works compared to giving combination chemotherapy alone in treating patients with previously untreated aggressive stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Compare the complete response rate (confirmed or unconfirmed) in patients with previously untreated aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with vs without gemcitabine. Secondary Compare the safety profile of these regimens in these patients. Compare the feasibility of these regimens, defined as the proportion of courses given as scheduled, in these patients. Compare freedom from treatment failure in patients treated with these regimens. OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, International Prognostic Index score (0-2 vs 3-5), and histology (B cell vs T cell). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral or IV prednisone on days 1-5. Arm II: Patients receive CHOP chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity or progressive disease. Patients achieving partial response or complete or unconfirmed complete response receive an additional 5 courses of therapy (for a total of 8 courses). Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 76-82 patients (38-41 per treatment arm) will be accrued for this study within 2 years.

Official Title
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Gem-CHOP: A Randomized Phase II Study of Gemcitabine Combined With CHOP in Untreated Aggressive Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Small Intestine Cancer

Intervention / Treatment
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* Drug: CHOP regimen
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) of 1 of the following WHO subtypes: Diffuse large B large cell lymphoma (including all clinical and morphologic variants) Grade 3 follicular lymphoma Extranodal T/NK cell lymphoma, nasal type Enteropathy-type T cell lymphoma Hepato-splenic T cell lymphoma Peripheral T cell lymphoma, unspecified Angioimmunoblastic lymphoma Anaplastic large cell lymphoma, systemic type Stage II-IV disease At least 1 site of measurable disease (e.g., lymph node or lymph node mass) The following subtypes are not allowed: Mantle cell lymphoma Burkitt's lymphoma Precursor B or T cell lymphoma Primary cutaneous B or T cell lymphoma No CNS involvement by lymphoma PATIENT CHARACTERISTICS: Age 18 to 70 Performance status Not specified Life expectancy Not specified Hematopoietic WBC > 3,000/mm^3 Neutrophil count > 1,000/mm^3 Platelet count > 100,000/mm^3 Hepatic Bilirubin < 2.5 times normal (unless due to lymphoma) ALT and AST < 2.5 times normal (unless due to lymphoma) Renal Creatinine < 2.0 mg/dL Cardiovascular No severe cardiac disease that would preclude study participation or limit life expectancy Pulmonary FEV_1 and DLCO ≥ 75% of predicted (unless due to lymphoma) No severe pulmonary disease that would preclude study participation or limit life expectancy Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix No severe neurologic or metabolic disease that would preclude study participation or limit life expectancy No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent monoclonal antibodies Chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy No concurrent radiotherapy Surgery Not specified Other No prior cytotoxic agents No prior treatment for NHL No other concurrent anticancer therapy No other concurrent investigational drugs

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CHOP regimen|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response as assessed by Cheson criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by CTC 2.0 |  |  | 
| Proportion of courses given as scheduled |  |  | 
| Freedom from treatment failure as assessed by Cheson criteria |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, adult grade III lymphomatoid granulomatosis, small intestine lymphoma