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

NCT01493479 | Completed Phase 2 DMC

• 1 other identifier: 06_DOG05_33
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 7

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.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Time to disease progression

  Assessed 3 months post treatment, repeated assessment up to 5 years follow-up

• Response duration

  Assessed 3 months post treatment, repeated assessment up to 5 years follow-up

Study Arms (1)

Fractionated Initial Zevalin

EXPERIMENTAL

Drug: 90Y Ibritumomab tiuxetan; Drug: Rituximab

Interventions

90Y Ibritumomab tiuxetan DRUG

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.

Also known as: Zevalin

Fractionated Initial Zevalin

Rituximab DRUG

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.

Also known as: Mabthera

Fractionated Initial Zevalin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Bayer: collaborator

Study Sites (7)

Centre Hospitalier Universitaire de Lille

Lille, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, France

Location

Centre Henri Becquerel

Rouen, France

Location

St George's Hospital

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Poole Hospital NHS Foundation Trust

Poole, United Kingdom

Location

Southampton University Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24297953 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibritumomab tiuxetan; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Timothy Illidge, Prof

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lead Clinical Trial Manager

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: December 16, 2011
• Study Start: June 6, 2007
• Primary Completion: January 1, 2011
• Study Completion: November 6, 2015
• Last Updated: October 15, 2019

Record last verified: 2019-10

Locations

FR (3); GB (4)