Zevalin® First Line in Follicular Lymphoma

NCT00772655 | Unknown Phase 2 DMC

• 3 other identifiers: EudraCT-No.:2006-005778-34PEI-No.: 364/01BFS-No.: 22461/2-2007-001
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Follicular Lymphoma

Keywords

Follicular Lymphoma; First line therapy; Zevalin; 90Yttrium-Ibritumomab Tiuxetan; Yttrium; Rituximab; Radio-immuno therapy

Outcome Measures

Primary Outcomes (1)

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

  6 months from entry onto trial

Secondary Outcomes (3)

• Time to progression after treatment with 90Y-Ibritumomab Tiuxetan

  5 years from entry onto trial

• 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

• Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients

  5 years from entry onto trial

Study Arms (1)

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; Drug: Rituximab

Interventions

90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab DRUG

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).

Also known as: Zevalin®, Mabthera®

Study Therapy

Rituximab DRUG

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.

Also known as: Mabthera®

Study Therapy

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Related Publications (2)

• 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.

  PMID: 35150296 DERIVED

• 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.

  PMID: 23233718 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibritumomab tiuxetan; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Antonio Pezzutto, Prof.

  Dept. of Hematology, Charité Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Christian Scholz, PD

  Dept. of Hematology, Charité Berlin, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. Christian Scholz

Study Record Dates

• First Submitted: October 14, 2008
• First Posted: October 15, 2008
• Study Start: October 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2015
• Last Updated: August 2, 2012

Record last verified: 2012-07