Abbreviated R-CHOP in Completely Excised Stage I or II DLBCL

Study Overview
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Brief Summary
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This study aims; to assess the efficacy of shortened systemic chemotherapy in patients with completely excised CD20 positive Diffuse Large B-cell Lymphoma (DLBCL) with Ann Arbor Stage I or II.

Detailed Description
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Unlike the limited stage diffuse Large B-cell Lymphoma (DLBCL) treated with primary chemotherapy followed by radiotherapy, patients with stage I or II DLBCL would be treated with surgical resection followed by chemotherapy in this trial. While chemotherapy is the main treatment modality and radiotherapy becomes adjuvant treatment in the former treatment scheme, surgical resection will remove all the gross lesions and chemotherapy aims to remove all microscopic disease whichever exists in the latter treatment scheme. Currently, six cycles of chemotherapy is usually performed after surgery even without any residual lesion compared with three cycles of chemotherapy in the former treatment scheme which plays primary role in the treatment scheme. The investigators will investigate whether abbreviated 3 cycles of Rituximab Plus Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone (R-CHOP) immunochemotherapy following complete resection is an effective and safe treatment.

Official Title
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Phase 2 Study of Abbreviated 3 Cycles of Rituximab Plus CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) Immunochemotherapy in Patients With Completely Excised Stage I or II CD20+ Diffuse Large B-cell Lymphoma

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Rituximab plus CHOP Immunochemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who underwent curative resection of primary tumor Pathologically confirmed CD20 positive diffuse large B-cell lymphoma (DLBCL) after surgical resection Ann Arbor Stage I or II No history of chemotherapy Performance status: ECOG 0-2 Age: 18 to 70 years old Complete excision with negative resection margin on pathologic report after surgery Cardiac ejection fraction ≥ 50% as measured by MUGA or 2D echocardiography without clinically significant abnormalities Adequate renal function: serum creatinine level below 2 mg/dL (177μmol/L) Adequate liver functions: Transaminase (AST/ALT) < 3X upper normal value, Bilirubin < 2X upper normal value Adequate hematologic function: hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500/mm3 and platelet count ≥ 75,000/mm3 Informed consent Exclusion Criteria: Patients with a known history of HIV (+) or HCV (+). However, HBV(+) patients are eligible if primary prophylaxis is given Previous or concurrent cancer that is distinct in primary site or histology from DLBCL, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions Unstable cardiac disease (i.e. congestive heart failure, arrhythmia symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry History of significant neurological or psychiatric disorders including dementia or seizures Active uncontrolled infection (viral, bacterial or fungal infection) Other serious medical illnesses Known hypersensitivity to any of the study drugs or their ingredients Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy Patient with B symptoms or Bulky disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Rituximab plus CHOP Immunochemotherapy<br>Interventions: conventional R-CHOP every 3 weeks for 3 cycles Rituximab 375 mg/M2 IV day 1 Cyclophosphamide 750 mg/M2 IV day1 Vincristine 1.5 mg/M2 (max. 2 mg) IV day1 Prednisolone 50 mg bid day 1-5, every 3 weeks | Drug: Rituximab plus CHOP Immunochemotherapy<br>* The R-CHOP treatment will continue up to 3 cycles with interval of 21 days: Each cycle consists of rituximab 375mg/m2 (iv, on day 1), cyclophosphamide 750 mg/m2 (iv, on day 1), doxorubicin 50mg/m2 (iv, on day 1), vincristine 1.4mg/m2 (iv, on day 1), and prednisolone 100mg (po, on day 1-5).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Proportion of patients surviving 2 years after first R-CHOP chemotherapy with no relapse of DLBCL | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | proportion of patients surviving at 2 year after first cycle of R-CHOP chemotherapy regardless of relapse of DLBCL | 2 years | 
| any adverse events as a measure of safety and tolerability | The number of patients with adverse events will be measured during R-CHOP chemotherapy according to CTCAE version 3.0. | from the first R-CHOP to 1 month after completion of R-CHOP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diffuse large B-cell lymphoma, rituximab, CHOP, abbreviated therapy