Zevalin® First Line in Follicular Lymphoma - Full Text View

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00772655

Purpose

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.

Condition	Intervention	Phase
Follicular Lymphoma	Drug: 90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab Drug: Rituximab	Phase II

MedlinePlus related topics: Lymphoma

Drug Information available for: Rituximab Ibritumomab tiuxetan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
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

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan [ Time Frame: 6 months from entry onto trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to progression after treatment with 90Y-Ibritumomab Tiuxetan [ Time Frame: 5 years from entry onto trial ] [ Designated as safety issue: No ]
Ability of consolidation therapy with Rituximab to induce molecular remission for CR patients not achieving molecular remission within 6 months after 90Y-Ibritumomab Tiuxetan [ Time Frame: 5 years from entry onto trial ] [ Designated as safety issue: No ]
Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients [ Time Frame: 5 years from entry onto trial ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Study Therapy: Experimental Induction therapy with a single course of 90Yttrium-Ibritumomab Tiuxetan (according to the standard procedure that includes Rituximab 250 mg/m2 plus 111Indium-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 up to a maximal dose of 12.000 MBq [if platelets are below 150000/µl only 11 MBq/kg are administered). Observation for patients achieving complete clinical and molecular response or partial clinical response. 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 (t14;18)-positivity 6 months after 90Y-Ibritumomab Tiuxetan.	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). Drug: 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.

Arms

Assigned Interventions

Study Therapy: Experimental

Induction therapy with a single course of 90Yttrium-Ibritumomab Tiuxetan (according to the standard procedure that includes Rituximab 250 mg/m2 plus 111Indium-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 up to a maximal dose of 12.000 MBq [if platelets are below 150000/µl only 11 MBq/kg are administered). Observation for patients achieving complete clinical and molecular response or partial clinical response. 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 (t14;18)-positivity 6 months after 90Y-Ibritumomab Tiuxetan.

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).

Drug: 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.

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

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772655

Contacts

Contact: Antonio Pezzutto, Prof.

+49 (0)30 450 553 ext 192

antonio.pezzutto@charite.de

Locations

Germany
Dept. of Hematology Oncology, Charité, Campus Virchow Klinikum Charité	Recruiting
Berlin, Germany, D-13353
Contact: Clinical study center +49 (0)30 450 553 ext 862 margrit.stodder@charite.de
Contact: Antonio Pezzutto, Prof. +49(0)30 450 553 ext 192 antonio.pezzutto@charite.de
Sub-Investigator: Kristina Lerch, MD

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator:	Antonio Pezzutto, Prof.	Dept. of Hematology, Charité Berlin, Germany
Study Director:	Christian Scholz, PD	Dept. of Hematology, Charité Berlin, Germany

More Information

Responsible Party:	Charité University, Berlin, Germany ( Prof. Dr. A. Pezzutto - Dept. of Hematology, Campus Virchow Klinikum, Charité Berlin )
Study ID Numbers:	EudraCT-No.:2006-005778-34, PEI-No.: 364/01, BFS-No.: 22461/2-2007-001
Study First Received:	October 14, 2008
Last Updated:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00772655
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

Follicular Lymphoma
First line therapy
Zevalin
90Yttrium-Ibritumomab Tiuxetan

Yttrium
Rituximab
Radio-immuno therapy

Study placed in the following topic categories:

Antibodies, Monoclonal
Lymphatic Diseases
Antibodies
Immunoproliferative Disorders
Rituximab
Lymphoma, Follicular

Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Follicular lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009