A phase III, open-label, prospective, two armed multicenter, randomized, group sequential study to evaluate the efficacy and safety of subsequent treatment with the Zevalin (ibritumomab tiuxetan) study regimen versus observation in patients with diffuse large B-cell lymphoma who are in complete remission after first-line CHOP-rituximab therapy. - ND

Conditions: Patients with remission induced (complete remission (CR) or unconfirmed complete remission (CRu) stage II, III or IV diffuse large B-cell lymphoma (DLBCL) according to the Revised European American Lymphoma (REAL)/World Health Organization (WHO) classification
MedDRA version: 9.1Level: LLTClassification code 10025310Term: Lymphoma

Registration Number: EUCTR2005-001727-11-IT

Lead Sponsor: SCHERING

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 400

Inclusion Criteria

1. Histologically confirmed, Ann Arbor stage II, III, or IV diffuse large B-cell lymphoma (DLBCL) according to the Revised European American Lymphoma (REAL)/World Health Organization (WHO) classification (from initial diagnosis made prior to starting CHOP-R therapy) 2. Central pathology review confirming the DLBCL diagnosis and CD20 positivity, and no evidence of DLBCL in bone marrow 3 First-line treatment of DLBCL must have been 6 or 8 cycles of standard CHOP chemotherapy (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 up to a maximum of 2 mg on day 1, and at least 40 mg/ m2 /day prednisone on days 1 to 5 every three weeks) in combination with rituximab (375 mg/m2) 4 Complete remission (CR) or unconfirmed complete remission (CRu) according to the International Workshop Response Criteria for NHL described by Cheson at all. and modified for this stady after first-line treatment with CHOP-R. (CT scans of thorax, abdomen, pelvis and neck-if applicable) must have been performed within 6 weeks after the last dose of the last course of CHOP-R. Applicability of the neck CT means that the patient had involvement on the neck region by palpation/physical esamination at 1st dignosis. 5 Central radiographic review of the CT scans (chest, abdomen, pelvis and if applicable neck) from before and after first-line treatment with CHOP-R fulfilling the radiological requirements for CR/CRu 6 Patients 60 years of age or older at time of randomization. 7 WHO performance status (PS) of 0 to 2 within 1 week of randomization 8 Absolute neutrophil count (ANC) equale or more than 1.5 x 109/l within 1 week of randomization 9 Hemoglobin (Hgb) equal or more than 10; 9 g/dL within 1 week of randomization 10 Platelets equal or more than 150 x 109/l within 1 week of randomization 11 Life expectancy of 3 months or longer 12 Written informed consent obtained according to local guidelines
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Presence of any other malignancy or history of prior malignancy except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma 2. Prior radioimmunotherapy, radiation therapy, or any other NHL therapy except first-line CHOP-rituxumab 3. Presence of gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis 4. Hystological transformation of low-grade NHL 5. Known seropositivity for HEPATITIS C Virus (HCV) or HEPATITIS B surface antigen(HbsAg) 6. Known history of HIV infection 7. Abnormal liver function: total bilirubin > 1.5 x ULN or ALT > 2.5 x ULN within one week of randomization 8. Abnormal renal function: serum creatinine > 2.0 x ULN 9. Nonrecovery from the toxic effects of CHOP-rituxumab therapy 10. Known hypersensitivity to murine or chimeric antibodies or proteins 11. G-CSF or GM-CSF therapy within two weeks (or four weeks if pegylated) prior to screening laboratory sampling 12. Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study 13. Male and female patients of child-bearing potential unwilling to practice effective contraception during the study and unwilling or unable to continue contraception for 12 months after their last dose of study treatment 14. Female patients who are pregnant or are currently breastfeeding 15. Treatment with investigational drugs less than 4 weeks before the planned day 1 or nonrecovery from the toxic effects of such therapy 16. Surgery less than 4 weeks before the planned Day1 or nonrecovery from the side effects of such surgery 17. Systemic concurrent corticosteroid use for any reason except as premedication in case of known or suspected allergies to contrast media or as premedication for potential side effects of rituximab treatment 18. Unwillingness or inability to comply with the protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of the Zevalin study regimen to compare with observation alone in patients with DLBCL who are in complete remission (CR or CRu) after first-line CHOP-R. Overall survival (OS) will be the primary end point;Secondary Objective: Disease-free survival (DFS) will be the secondary endpoint. An additional secondary endpoint will be health related quality of life (HRQL) as assessed by the patient using standard questionnaires (FACT-G and EuroQoL EQ-5D).;Primary end point(s): Overall survial

Secondary Outcome Measures