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

October 11, 2019 updated by: Emmie Taylor, The Christie NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France
        • Centre Hospitalier Universitaire De Lille
      • Nantes, France
        • Centre Hospitalier Universitaire De Nantes
      • Rouen, France
        • Centre Henri Becquerel
  • United Kingdom
      • London, United Kingdom
        • St George's Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie Nhs Foundation Trust
      • Poole, United Kingdom
        • Poole Hospital NHS Foundation Trust
      • Southampton, United Kingdom
        • Southampton University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fractionated Initial Zevalin
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.
Other Names:
  • Zevalin
Drug: 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.

Other Names:
  • Mabthera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: Assessed 3 months post treatment
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Assessed 3 months post treatment
Combined Complete Response rate
Time Frame: Assessed 3 months post treatment
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Assessed 3 months post treatment
Partial Response Rate
Time Frame: Assessed 3 months post treatment
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
Time Frame: Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
Response duration
Time Frame: Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Christie NHS Foundation Trust

Collaborators

Bayer

Investigators

  • Principal Investigator: Timothy Illidge, Prof, The Christie Nhs Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2007

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

November 6, 2015

Study Registration Dates

First Submitted

December 14, 2011

First Submitted That Met QC Criteria

December 15, 2011

First Posted (Estimate)

December 16, 2011

Study Record Updates

Last Update Posted (Actual)

October 15, 2019

Last Update Submitted That Met QC Criteria

October 11, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06_DOG05_33

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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