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 (CHOP-R) therapy - Zevalin in aggressive lymphoma (DLBCL) phase III

Conditions: Diffuse large B-cell lymphoma

Registration Number: EUCTR2005-001727-11-AT

Lead Sponsor: Schering AG, Global Medical Development

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 DLBCL according to
the REAL/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, with generally accepted
adjustments in dose or frequency due to toxicity, patient scheduling, etc.) 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 et al
and modified for this study (see Appendix 2) after first-line treatment with CHOP-
R. CT scans of chest, 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 of the neck
region by palpation / physical examination at first diagnosis

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) > 1.5 x 109/L within 1 week of randomization

9. Hemoglobin (Hgb) > 10 g/dL within 1 week of randomization

10. Platelets > 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-R

3. Presence of gastric, central nervous system (CNS), or testicular lymphoma at
first diagnosis

4. Histological 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 1
week of randomization

8. Abnormal renal function: serum creatinine > 2.0 x ULN within 1 week of
randomization

9. Nonrecovery from the toxic effects of CHOP-R 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 Day 1 or nonrecovery from the
side effects of such surgery

17. 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 compared 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 endpoint.;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 survival

Secondary Outcome Measures