Clinical trial NCT01493479: Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as an Initial Therapy of Follicular Lymphoma
Official title: Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Follicular Lymphoma
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2011-12-16
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall response rate
timeFrame: Assessed 3 months post treatment
measure: Combined Complete Response rate
timeFrame: Assessed 3 months post treatment
measure: Partial Response Rate
timeFrame: Assessed 3 months post treatment
Secondary outcomes:
measure: Time to disease progression
timeFrame: Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
measure: Response duration
timeFrame: Assessed 3 months post treatment, repeated assessment up to 5 years follow-up
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Rouen
country: France
facility: Centre Henri Becquerel
city: London
country: United Kingdom
facility: St George's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Poole
country: United Kingdom
facility: Poole Hospital NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Timothy Illidge, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.