search
Back to results

Zevalin® First Line in Follicular Lymphoma

Primary Purpose

Follicular Lymphoma

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab
Rituximab
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring Follicular Lymphoma, First line therapy, Zevalin, 90Yttrium-Ibritumomab Tiuxetan, Yttrium, Rituximab, Radio-immuno therapy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Study Therapy

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan

    Secondary Outcome Measures

    Time to progression after treatment with 90Y-Ibritumomab Tiuxetan
    Ability of consolidation therapy with Rituximab to induce molecular remission for CR patients not achieving molecular remission within 6 months after 90Y-Ibritumomab Tiuxetan
    Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients

    Full Information

    First Posted
    October 14, 2008
    Last Updated
    July 31, 2012
    Sponsor
    Charite University, Berlin, Germany
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00772655
    Brief Title
    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

    2. Study Status

    Record Verification Date
    July 2012
    Overall Recruitment Status
    Unknown status
    Study Start Date
    October 2007 (undefined)
    Primary Completion Date
    June 2010 (Actual)
    Study Completion Date
    June 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Charite University, Berlin, Germany

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Follicular Lymphoma
    Keywords
    Follicular Lymphoma, First line therapy, Zevalin, 90Yttrium-Ibritumomab Tiuxetan, Yttrium, Rituximab, Radio-immuno therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    60 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Study Therapy
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab
    Other Intervention Name(s)
    Zevalin®, Mabthera®
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Rituximab
    Other Intervention Name(s)
    Mabthera®
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan
    Time Frame
    6 months from entry onto trial
    Secondary Outcome Measure Information:
    Title
    Time to progression after treatment with 90Y-Ibritumomab Tiuxetan
    Time Frame
    5 years from entry onto trial
    Title
    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
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Pezzutto, Prof.
    Organizational Affiliation
    Dept. of Hematology, Charité Berlin, Germany
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Christian Scholz, PD
    Organizational Affiliation
    Dept. of Hematology, Charité Berlin, Germany
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    35150296
    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.
    Results Reference
    derived
    PubMed Identifier
    23233718
    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.
    Results Reference
    derived

    Learn more about this trial

    Zevalin® First Line in Follicular Lymphoma

    We'll reach out to this number within 24 hrs