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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

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

NCT ID

NCT00772655

First Posted

October 14, 2008

Last Updated

July 31, 2012

Sponsor

Charite University, Berlin, Germany

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

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

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

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Zevalin® First Line in Follicular Lymphoma

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