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

Follicular Lymphoma Clinical Trial

— FIZZ  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01493479
• Other study ID #: 06_DOG05_33
• Status: Completed
• Phase: Phase 2
• Start date: June 6, 2007
• Est. completion date: November 6, 2015

Study information

• Verified date: October 2019
• Source: The Christie NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: November 6, 2015
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• 90Y Ibritumomab tiuxetan
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.
• Rituximab
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.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Lille	Lille
France	Centre Hospitalier Universitaire de Nantes	Nantes
France	Centre Henri Becquerel	Rouen
United Kingdom	St George's Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Poole Hospital NHS Foundation Trust	Poole
United Kingdom	Southampton University Hospital	Southampton

Sponsors (2)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust	Bayer

Countries where clinical trial is conducted

France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.	Assessed 3 months post treatment
Primary	Combined Complete Response rate	According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.	Assessed 3 months post treatment
Primary	Partial Response Rate	According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.	Assessed 3 months post treatment
Secondary	Time to disease progression		Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
Secondary	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