Zevalin® First Line in Follicular Lymphoma

Follicular Lymphoma Clinical Trial

Official title:

Multicenter European Pilot Study of 90Yttrium-Ibritumomab Tiuxetan as First Line Therapy for Stage III - IV Follicular Lymphoma (and Selected Patients With Extended Stage II) Followed by Consolidation Rituximab for Patients in Complete Remission But With Persistent Molecular Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00772655
• Other study ID #: EudraCT-No.:2006-005778-34
• Secondary ID: PEI-No.: 364/01B
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 14, 2008
• Last updated: July 31, 2012
• Start date: October 2007
• Est. completion date: June 2015

Study information

• Verified date: July 2012
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This is a European multicenter study of 90Yttrium-Ibritumomab Tiuxetan (90Y-Ibritumomab Tiuxetan) (Zevalin®) as a front line therapy for patients with follicular lymphoma grade I-IIIa and stage III-IV (as well as for selected patients with extended abdominal stage II). For patients with complete clinical remission but persistent molecular disease subsequent to 90Y-Ibritumomab Tiuxetan treatment a consolidation immunotherapy with Rituximab is added, to eradicate minimal residual disease.

Description:

Only patients requiring treatment (B-symptoms, lymphoma progression > 50% within an observation period of 6 months or less, organ compression by lymphoma or bulky disease as defined by lesions above 5 cm on one axis) may enter the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: June 2015
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Patient > 50 years old

• Follicular lymphoma grade I, II, or IIIa according to REAL/WHO classification

• Ann Arbor stage III, or IV, or stage II with disseminated abdominal disease requiring extensive abdominal irradiation

• No prior chemotherapy, immunotherapy, or irradiation. Furthermore, when receiving therapy as part of this "Zevalin® first line in follicular lymphoma" trial and up to six months after therapy has ended, patients may not participate in another clinical trial. If patients receive consolidation therapy with Rituximab, the six months period is counted from the end of the consolidation therapy.

• Lymphoma cells positive for CD20

• Measurable disease (two perpendicular diameters by either physical or radiological examination)

• WHO/ECOG performance status 0 - 2

• Written informed consent

Exclusion Criteria:

• Bone marrow involvement only

• Bone marrow infiltration > 25%

• Leukocytopenia < 2.500 /µl

• Thrombocytopenia < 100.000 /µl

• Bulk lesions > 10 cm

• CNS lymphoma manifestation

• Circulating tumor cells > 500 /µl

• Extensive pleural effusion/ascites (> 1000 ml as estimated by ultrasound/CT)

• Severe concomitant diseases (e.g. congestive heart failure, myocardial infarction within 6 months of study, severe uncontrolled hypertension, renal insufficiency requiring hemodialysis, pulmonary disease, liver disease)

• Abnormal liver function: transaminases or total bilirubin > 2 x upper limit of normal (ULN) (unless caused by the lymphoma)

• Abnormal renal function: serum creatinine > 2 x upper limit of normal (unless caused by the lymphoma)

• Previous malignancy other than non-melanoma skin cancer

• Pregnant or breast feeding female patients (negative pregnancy test required for women of fertile age), no effective contraception

• HIV positivity

• Known hypersensitivity to foreign proteins, murine antibodies, presence of human anti-murine antibodies (HAMA) reactivity

• Severe psychiatric illness

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• 90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab
A single course of 90Y-Ibritumomab Tiuxetan (according to the standard procedure that includes Rituximab 250 mg/m2 plus 111In-Ibritumomab Tiuxetan for dosimetry on day one followed by Rituximab 250 mg/m2 and 90Y-Ibritumomab Tiuxetan 15 MBq/kg on day 8 or 9 [if platelets are below 150000/µl only 11 MBq/kg are administered).
• Rituximab
Consolidation/maintenance therapy with 4 weekly courses of Rituximab 375 mg/m2 followed by 4 bimonthly courses of Rituximab 375 mg/m2 for patients in clinical CR but with persistent Bcl-2-positivity 6 months after 90Y-Ibritumomab Tiuxetan.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan		6 months from entry onto trial	No
Secondary	Time to progression after treatment with 90Y-Ibritumomab Tiuxetan		5 years from entry onto trial	No
Secondary	Ability of consolidation therapy with Rituximab to induce molecular remission for CR patients not achieving molecular remission within 6 months after 90Y-Ibritumomab Tiuxetan		5 years from entry onto trial	No
Secondary	Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients		5 years from entry onto trial	Yes