Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving more than one drug (combination chemotherapy) together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying giving gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone together with rituximab to see how well it works in treating patients with newly diagnosed diffuse large B-cell lymphoma.

Detailed Description
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OBJECTIVES: To determine whether rituximab, in combination with non-cardiotoxic chemotherapy comprising gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone, is efficacious in a group of patients who are unfit for CHOP chemotherapy. OUTLINE: This is a multicenter study. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8; cyclophosphamide IV, vincristine sulfate IV, and rituximab IV on day 1; and oral prednisolone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Official Title
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A Phase II Multicentre Trial of Gemcitabine, CVP, and Rituximab (R-GCVP) for the Treatment of Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma, Considered Unsuitable for R-CHOP Chemotherapy

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide
* Drug: gemcitabine hydrochloride
* Drug: prednisolone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed CD20-positive diffuse large B-cell non-Hodgkin lymphoma (DLBCL) according to the current WHO classification, including all morphological variants Newly diagnosed disease Bulky stage IA-IV disease No non-bulky stage IA disease Measurable disease Not eligible for CHOP chemotherapy due to impaired cardiac function Cardiac status that does not allow the administration of 8 courses of R-CHOP chemotherapy, as defined by 1 of the following criteria: Ejection fraction less than 50% as assessed by either ECHO or MUGA scan NYHA class III-IV No high-grade transformation of low-grade lymphoma No symptomatic central nervous system or meningeal involvement by the lymphoma No AIDS-related lymphoma PATIENT CHARACTERISTICS: ECOG performance status 0-3 Life expectancy > 3 months Platelet count > 100 x 10^9/L WBC > 3 x 10^9/L Neutrophils > 1.5 x 10^9/L (unless elevated level attributed to bone marrow infiltration by lymphoma) Serum bilirubin < 50 μmol/L Transaminases < 2.5 times upper limit of normal (unless elevated level attributed to lymphoma) Glomerular filtration rate > 30 mL/min Not pregnant or nursing Fertile patients must use effective contraception No other concurrent uncontrolled medical condition No active malignant disease, other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix, within the past 10 years No positive serology for HIV No medical or psychiatric conditions that compromise the patient's ability to give informed consent PRIOR CONCURRENT THERAPY: No prior chemotherapy, radiotherapy, or other investigational drug for this indication

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-GCVP<br>Up to 6 x 21 day cycles of R-GCVP: Gemcitabine 750mg/m^2 days 1 & 8 (increasing to 875mg/m^2 for cycle 2 & 1g/m^2 for subsequent cycles if tolerated satisfactorily) Cyclophosphamide 750mg/m^2 day 1 Vincristine 1.4mg/m^2 day 1 (capped at 2mg) Prednisolone 100mg/day days 1-5 Rituximab 375mg/m^2 day 1 Neulasta 6mg day 9 | Biological: rituximab<br> <br> Drug: cyclophosphamide<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: prednisolone<br> <br> Drug: vincristine sulfate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | End of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | End of treatment | 
| Progression-free survival |  | Not specified in protocol | 
| Overall survival |  | Not specified in protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult diffuse large cell 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