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

Primary Purpose

Follicular Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
90Y Ibritumomab tiuxetan
Rituximab
Sponsored by
The Christie NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centre Hospitalier Universitaire de Lille
  • Centre Hospitalier Universitaire de Nantes
  • Centre Henri Becquerel
  • St George's Hospital
  • The Christie NHS Foundation Trust
  • Poole Hospital NHS Foundation Trust
  • Southampton University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fractionated Initial Zevalin

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Combined Complete Response rate
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Partial Response Rate
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.

Secondary Outcome Measures

Time to disease progression
Response duration
To be assessed for patients achieving a response, including assessment of overall survival and time until next treatment.

Full Information

First Posted
December 14, 2011
Last Updated
October 11, 2019
Sponsor
The Christie NHS Foundation Trust
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT01493479
Brief Title
Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as an Initial Therapy of Follicular Lymphoma
Acronym
FIZZ
Official Title
Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
June 6, 2007 (Actual)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
November 6, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Christie NHS Foundation Trust
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fractionated Initial Zevalin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
90Y Ibritumomab tiuxetan
Other Intervention Name(s)
Zevalin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate
Description
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Time Frame
Assessed 3 months post treatment
Title
Combined Complete Response rate
Description
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Time Frame
Assessed 3 months post treatment
Title
Partial Response Rate
Description
According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999.
Time Frame
Assessed 3 months post treatment
Secondary Outcome Measure Information:
Title
Time to disease progression
Time Frame
Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
Title
Response duration
Description
To be assessed for patients achieving a response, including assessment of overall survival and time until next treatment.
Time Frame
Assessed 3 months post treatment, repeated assessment up to 5 years follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Illidge, Prof
Organizational Affiliation
The Christie NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Universitaire de Lille
City
Lille
Country
France
Facility Name
Centre Hospitalier Universitaire de Nantes
City
Nantes
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
Country
France
Facility Name
St George's Hospital
City
London
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Poole Hospital NHS Foundation Trust
City
Poole
Country
United Kingdom
Facility Name
Southampton University Hospital
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
24297953
Citation
Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated (9)(0)Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. doi: 10.1200/JCO.2013.50.3110. Epub 2013 Dec 2.
Results Reference
derived

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

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