Zevalin® First Line in Follicular Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Christian Scholz M.D., Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00772655
First received: October 14, 2008
Last updated: July 31, 2012
Last verified: July 2012
  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 2

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

Resource links provided by NLM:


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: June 2015
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Therapy
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).
Other Names:
  • Zevalin®
  • Mabthera®
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.
Other Name: Mabthera®

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided by Charite University, Berlin, Germany

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christian Scholz M.D., PD Dr. med. Christian Scholz, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT00772655     History of Changes
Other 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: July 31, 2012
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014