Randomized phase III study on the effect of early intensification of rituximab in combination with 2-weekly CHOP chemotherapy followed by rituximab maintenance in elderly patients (66-80 years) with diffuse large B-cell lymphoma - HOVON 84 NH

Phase 1

• Conditions: Diffuse large B-cell lymphoma

• Registration Number: EUCTR2006-005174-42-DK
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-08-01
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

For first randomization:
•Patients with a confirmed histologic diagnosis of diffuse large B-cell lymphoma (DLBCL) based upon a representative histology specimen according to the WHO classification (see appendix A)
•DLBCL must be CD20 positive
•Ann Arbor stages II-IV (see appendix C)
•Age = 66 and ? 80 years
•WHO performance status 0 – 2 (see appendix E)
•Written informed consent

For second randomization:
Patients achieving a CR (or FDG-PET negative PR/CRu) after 8 cycles of R-CHOP14 will be randomized to maintenance treatment with rituximab or no further treatment.
•Patients in complete remission or FDG-PET negative partial remission/unconfirmed complete remission at least 4 weeks after the last of 8 cycles of R-CHOP14
•Time interval since last cycle of R-CHOP14 between 4 and 8 weeks
•No rituximab-related adverse event necessitating stopping of rituximab administration
•No active infection
•Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
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

•Intolerance of exogenous protein administration
•Severe cardiac dysfunction (NYHA classification III-IV, see appendix F) or LVEF < 45%
Congestive heart failure or symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication. Myocardial infarction during the last 6 months
•Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value) unless clearly related to NHL involvement
•Patients with uncontrolled asthma or allergy, requiring systemic steroid treatment
•Significant hepatic dysfunction (total bilirubin ? 30?mol/l or transaminases = 2.5 x upper normal limit), unless related to NHL
•Significant renal dysfunction (serum creatinine = 150 umol/l or clearance = 60 ml/min), unless related to NHL
•Clinical signs of severe cerebral dysfunction
•Suspected or documented Central Nervous System involvement by NHL
•Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
•Testicular DLBCL
•Primary mediastinal B cell lymphoma
•Transformed indolent lymphoma
•(EBV) post-transplant lymphoproliferative disorder
•Secondary lymphoma after previous chemotherapy or radiotherapy
•Major surgery, other than diagnostic surgery, within the last 4 weeks
•Patients with active uncontrolled infections
•Patients known to be HIV-positive
•Active chronic hepatitis B or C infection
•Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease)
•Life expectancy < 6 months
•Prior treatment with chemotherapy, radiotherapy or immunotherapy for this lymphoma, except a short course of prednisone (< 1 week) and/or cyclophosphamide (< 1 week and not in excess of 900 mg/m2 cumulative) or local radiotherapy in order to control life threatening tumor related symptoms
•History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess in a prospective, multicenter, randomized phase III study in elderly patients with DLBCL:<br>•the effect of early intensification of rituximab combined with 2-weekly CHOP +G-CSF (CHOP14) in comparison to no intensification of rituximab on the response rate (complete remission and FDG-PET negative partial remission/unconfirmed complete remission) and time to reach response<br>;Secondary Objective: To assess in a prospective, multicenter, randomized phase III study in elderly patients with DLBCL<br>•the efficacy of maintenance treatment with rituximab in comparison to no further treatment on failure free survival<br><br>;Primary end point(s): Response rate ( complete remission and FDG-PET negative patial remission or unconfirmed complee remission)