Clinical trial NCT00772655: Zevalin® First Line in Follicular Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Follicular Lymphoma
Keywords: Follicular Lymphoma
First line therapy
Zevalin
90Yttrium-Ibritumomab Tiuxetan
Yttrium
Rituximab
Radio-immuno therapy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2008-10-15
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan
timeFrame: 6 months from entry onto trial
Secondary outcomes:
measure: Time to progression after treatment with 90Y-Ibritumomab Tiuxetan
timeFrame: 5 years from entry onto trial
measure: Ability of consolidation therapy with Rituximab to induce molecular remission for CR patients not achieving molecular remission within 6 months after 90Y-Ibritumomab Tiuxetan
timeFrame: 5 years from entry onto trial
measure: Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients
timeFrame: 5 years from entry onto trial
Other outcomes:
Locations:
Study officials:
affiliation: Dept. of Hematology, Charité Berlin, Germany
name: Antonio Pezzutto, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Hematology, Charité Berlin, Germany
name: Christian Scholz, PD
role: STUDY_DIRECTOR
References:
citation: Rieger K, De Filippi R, Linden O, Viardot A, Hess G, Lerch K, Neumeister P, Stroux A, Peuker CA, Pezzutto A, Pinto A, Keller U, Scholz CW. 90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years. Ann Hematol. 2022 Apr;101(4):781-788. doi: 10.1007/s00277-022-04781-3. Epub 2022 Feb 12.
citation: Scholz CW, Pinto A, Linkesch W, Linden O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. (90)Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. doi: 10.1200/JCO.2011.41.1553. Epub 2012 Dec 10.