Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin 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. Giving epratuzumab and rituximab together may be more effective in treating follicular non-Hodgkin lymphoma. PURPOSE: This phase II trial is studying how well giving epratuzumab together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Primary To determine the response rate (overall and complete) after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular non-Hodgkin lymphoma (NHL). To determine the time to progression after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL. Secondary To determine the toxicity profile of epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL. To establish whether the therapeutic effects of the combination of epratuzumab and rituximab are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone). To determine the relationship between the change in fludeoxyglucose F 18 uptake early after epratuzumab and rituximab treatment with response rate and time to progression. OUTLINE: Induction therapy (month 1): Patients receive epratuzumab IV over 5-30 minutes on days 1, 8, 15, and 22 and rituximab IV on days 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity. Extended induction therapy (months 3, 5, 7, and 9): Patients receive epratuzumab IV over 5-30 minutes followed by rituximab IV in weeks 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity. Patients receive fludeoxyglucose F 18 (FDG) subcutaneously and undergo positron emission tomography at baseline and after induction therapy to assess the degree of FDG uptake. After completion of study treatment, patients are followed every 4 months for 2 years then every 6 months for up to 10 years.

Official Title
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A Phase II Trial of Extended Induction Epratuzumab (Anti-CD22 Monoclonal Antibody) (CALGB IND #XXXXX) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: epratuzumab
* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* confirmed follicular non-Hodgkin lymphoma (NHL) Previously untreated disease WHO classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II disease NOTE: *Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine-needle aspirates are not acceptable for diagnosis Confirmed CD20 antigen expression by flow cytometry or immunohistochemistry Measurable disease by physical examination or imaging studies Any tumor mass > 1 cm is acceptable No nonmeasurable disease only, including any of the following: Bone lesions Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Bone marrow (involvement by NHL should be noted) No known CNS involvement by lymphoma Required to participate in companion FDG-PET imaging study CALGB 580701 PATIENT CHARACTERISTICS: ECOG performance status ≤ 2 Absolute neutrophil count ≥ 1,000/μL Platelet count ≥ 50,000/μL Patients with HIV infection are eligible provided they meet the following criteria: No evidence of coinfection with hepatitis B or C CD4+ cell count ≥ 400/mm^3 No evidence of resistant strains of HIV If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL No history of AIDS-defining conditions Not pregnant or nursing Fertile patients must use effective contraception during and for 3 months after completion of study therapy No known Human Anti-Chimeric Antibody (HACA)-positivity PRIOR CONCURRENT THERAPY: No prior therapy for NHL including chemotherapy, radiotherapy, or immunotherapy (e.g., monoclonal antibody-based therapy) More than 2 weeks since prior corticosteroids except for maintenance therapy for non-malignant disease No concurrent dexamethasone or other steroids as antiemetics except for the following circumstances: Treatment of acute infusion reactions according to institutional procedures No concurrent hormonal therapy except steroids for adrenal failure OR hormones for non-disease-related conditions (e.g., insulin for diabetes) No other concurrent chemotherapeutic agents

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 Plus Rituximab<br>Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36 | Biological: epratuzumab<br>* Days 1, 8, 15, 22 and weeks 12, 20, 28, & 36: 360mg/sq m IV<br>Biological: rituximab<br>* Day 3, 8, 15, 22 and weeks 12, 20, 28, & 36: 375mg/sq m IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response | Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: >=50% decrease in the sum of the product of diameters of indicator lesions | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method. | Duration of study (up to 10 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II grade 1 follicular lymphoma, stage II grade 2 follicular lymphoma, stage II grade 3 follicular lymphoma, 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