Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as epratuzumab and 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.> PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma.

Detailed Description
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OBJECTIVES:> Primary> Assess the efficacy of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP), as measured by 12-month, event-free survival, in patients with previously untreated stage II, III, or IV diffuse large B-cell lymphoma.> Assess the use of positron emission tomography (PET) scan routinely early in treatment and after completion of treatment.> Assess the functional response rate (complete response, partial response, or stable disease by CT scan and PET negative) in patients treated with this regimen.> Assess the safety of this treatment regimen.> Secondary> Correlate laboratory prognostic factors for large cell lymphoma with clinical response to this regimen.> OUTLINE: This is a multicenter study.> Patients receive epratuzumab IV over 1 hour on day 1, rituximab IV over 4-8 hours on day 1 or days 1 and 2, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 or 2, and oral prednisone on days 1-5 or 2-6. 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 periodically for up to 5 years.> PROJECTED ACCRUAL: A total of 86 patients will be accrued for this study.>

Official Title
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A Phase II Study of Epratuzumab, Rituximab (ER)-CHOP for Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: epratuzumab
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diffuse large B-cell lymphoma B-cell phenotype (CD20+) as determined by immunohistochemistry (IHC) or flow cytometry Stage II, III, or IV disease CD22+ tumor by IHC* NOTE: *CD22 status may be determined after study enrollment Measurable disease, defined as at least 1 lesion ≥ 1.5 cm by CT scan or physical exam No relapsed or refractory non-Hodgkin's lymphoma No history of transformed lymphoma No CNS lymphoma CNS symptoms or bone marrow or sinus involvement must have absence of CNS lymphoma confirmed by lumbar puncture PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3 - For patients with ECOG PS 3, the PS must be disease related Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin ≤ 2 mg/dL (if total bilirubin > 2 mg/dL, direct bilirubin should be within normal limits) AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if there is liver involvement) Creatinine ≤ 2 times ULN Life expectancy ≥ 12 weeks Negative pregnancy test Not pregnant or nursing Fertile patients must use effective contraception during and for 12 months after completion of study treatment No active serious infection requiring antibiotics No New York Heart Association class III or IV heart disease No other primary malignancy within the past 5 years, except for squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or previously treated prostate cancer with a stable prostate-specific antigen No known HIV positivity No known hepatitis B or C infection Ejection fraction ≥ 45% by MUGA or echocardiogram (required if patients has a history of heart disease or is ≥ 50 years old) Willing to provide blood and tissue samples for mandatory translational research component of study PRIOR CONCURRENT THERAPY: No prior therapy for diffuse large B-cell lymphoma, including the following: Chemotherapy Immunotherapy Biologic therapy Radiotherapy Prior short course (≤ 14 days) of corticosteroids allowed Prior splenectomy allowed No prior pelvic irradiation No other concurrent investigational agents No concurrent chemotherapy, immunotherapy, or radiotherapy No concurrent enrollment on another treatment study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy)

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: Epratuzumab + Rituximab + CHOP<br>One arm open label. | Biological: epratuzumab<br> <br> Biological: rituximab<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisone<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 |
| --- | --- | --- |
| Event-free Survival After 12 Months | The primary endpoint of the trial was the percentage of the eligible patients who were alive and event-free 12 months after enrollment to the study (EFS12). | From Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Percentage of participants alive at different time points | time from study entry to 36 months | 
| Progression-free Survival (PFS) | Percentage of participants Progression-free at different time points. Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance. | the time from study entry to 36 months | 
| Overall Response Rate (ORR) | Overall response rate will be estimated by the number of patients with objective status of partial response (PR), unconfirmed complete response (CRu), or complete response (CR) during the first 6 cycles of treatment divided by number of evaluable patients (met eligibility criteria, signed consent form, and started treatment). Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance. | Baseline to first 6 cycles of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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