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

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.