Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as an Initial Therapy of Follicular Lymphoma

Study Overview
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Brief Summary
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90Y Ibritumomab tiuxetan (zevalin) has demonstrated consistently high response rates in patients who have received previous treatment for lymphoma. More than two-thirds of the patients who achieve CR go on to experience durable remissions lasting for years. Despite these highly promising clinical results with radioimmunotherapy (RIT) in relapsed follicular lymphoma there is very little data using RIT in previously untreated follicular lymphoma. The objective of this trial is to evaluate the safety and efficacy of two fractions of Zevalin in patients with previously untreated follicular lymphoma in a Phase II study.

Official Title
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Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin)

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: 90Y Ibritumomab tiuxetan
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a histologically confirmed CD20 +ve follicular lymphoma grades I to IIIa. Patients with at least one of the following symptoms requiring initiation of treatment: (as outlined by the modified BNLI/GELF criteria below) Nodal mass > 7cm in its greater diameter B symptoms Elevated serum LDH or beta2-microglobulin involvement of at least 3 nodal sites (each with a diameter > 3 cm) symptomatic splenic enlargement compressive syndrome Patients must have an ECOG performance status less than or equal to 2 and an anticipated survival of at least 6 months. Patients must have an absolute granulocyte count of above 1,500/mm3, and a platelet count of above 100,000/mm3 post 4 weeks of unlabelled Rituximab. A hemoglobin >= 8.0 g/dl Patients must have adequate renal function (defined as calculated creatinine clearance > 30 ml/mn), hepatic function (defined as total bilirubin <1.5 times upper limit of normal), and hepatic transaminases (defined as AST <5 times upper limit of normal) Patients must have given informed consent prior to study entry. Exclusion Criteria: Patients with a mean of >20% of the intratrabecular marrow space involved with lymphoma on bone marrow biopsy following induction Rituximab therapy. Transformed follicular lymphoma and discordant lymphoma Patients with active obstructive hydronephrosis. Patients with initial disease bulk greater than 10cm. Patients with evidence of active infection requiring i.v. antibiotics at the time of study entry. Patients with congestive heart failure stage III or IV of NYHA classification, myocardial infraction or unstable angina within 6 months or other serious illness that would preclude evaluation. Patients with left VEF < 40% Patients with large pleural or peritoneal effusions. Patients with known HIV infection or active HBV (HbsAg positivity) or HCV infection. Known Hypersensitivity to murine antibodies or proteins Patients who are pregnant or breast-feeding. Male and female patients must agree to use effective contraception for 12 months following 90Y-ibritumomab tiuxetan antibody therapy. Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer, cervical cancer in situ, or other cancer for which the patient has been disease-free for 5 years.

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: Fractionated Initial Zevalin<br> | Drug: 90Y Ibritumomab tiuxetan<br>* 2 x iv infusions of 11.1 MBq/kg. 1st infusion at week 1, 2nd during weeks 9-13. 2nd infusion may be reduced to 7.4MBq/kg in the case of grade 3 haematological toxicity following the 1st infusion.<br>* Other names: Zevalin;Drug: Rituximab<br>* All patients receive 2 x iv infusions of 250 mg/m2 Rituximab given 7-8 days apart prior to each zevalin infusion. The 2nd rituximab infusion is given immediately prior to Zevalin. In addition patients with greater than 20% bone marrow involvement at screening receive rituximab pretreatment prior to entering the main treatment phase of the trial, consisting of 4 x weekly iv doses of rituximab(375 mg/m2). This is followed by a repeat bone marrow biopsy, bone marrow involvement must have fallen to <= 20% to enter the main treatment phase of the trial.<br>* Other names: Mabthera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. | Assessed 3 months post treatment | 
| Combined Complete Response rate | According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. | Assessed 3 months post treatment | 
| Partial Response Rate | According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. | Assessed 3 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | Assessed 3 months post treatment, repeated assessment up to 5 years follow-up | 
| Response duration | To be assessed for patients achieving a response, including assessment of overall survival and time until next treatment. | Assessed 3 months post treatment, repeated assessment up to 5 years follow-up |