Randomised phase III study on the effect of early intensification of rituximab in combination with two-weekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy followed by rituximab maintenance in elderly patients (66 to 80 years) with diffuse large B-cell lymphoma

Phase 3

Completed

• Conditions: Diffuse large B-cell lymphoma; Cancer; Malignant neoplasms

• Registration Number: ISRCTN82286322
• Lead Sponsor: Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands) - Data Centre

Brief Summary

2020 Results article in https://pubmed.ncbi.nlm.nih.gov/32730183/ (added 07/10/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-08-23
• Study Completion: 2012-03-31
• Last Update Posted: 18 October 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Patients with a confirmed histological diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL) based upon a representative histology specimen according to the World Health Organisation (WHO) classification
2. DLBCL must be CD20 positive
3. Ann Arbor stages II - IV
4. Greater than or equal to 66 and less than or equal to 80 years
5. Age WHO performance status 0 to 2
6. Written informed consent

Exclusion Criteria

1. Intolerance of exogenous protein administration
2. Severe cardiac dysfunction (New York Heart Association [NYHA] classification III - IV or Left Ventricular Ejection Fraction [LVEF] less than 45%). Congestive heart failure or symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication. Myocardial infarction during the last six months
3. Severe pulmonary dysfunction (vital capacity or diffusion capacity less than 50% of predicted value) unless clearly related to Non-Hodgkin lymphoma (NHL) involvement
4. Patients with uncontrolled asthma or allergy, requiring systemic steroid treatment
5. Significant hepatic dysfunction (total bilirubin greater than or equal to 30mmol/l or transaminases greater than or equal to 2.5 x upper normal limit), unless related to NHL
6. Significant renal dysfunction (serum creatinine greater than or equal to 150 umol/l or clearance less than or equal to 60 ml/min), unless related to NHL
7. Clinical signs of severe cerebral dysfunction
8. Suspected or documented central nervous system involvement by NHL
9. 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
10. Testicular DLBCL
11. Primary mediastinal B cell lymphoma
12. Transformed indolent lymphoma
13. Epstein Barr Virus (EBV) lymphoproliferative disorder
14. Secondary lymphoma after previous chemotherapy or radiotherapy
15. Major surgery, other than diagnostic surgery, within the last four weeks
16. Patients with active uncontrolled infections
17. Patients known to be Human Immunodeficiency Virus (HIV)-positive
18. Active chronic hepatitis B or C infection
19. 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)
20. Life expectancy less than six months
21. Prior treatment with chemotherapy, radiotherapy or immunotherapy for this lymphoma, except a short course of prednisone (less than one week) and/or cyclophosphamide (less than one week and not in excess of 900 mg/m^2 cumulative) or local radiotherapy in order to control life threatening tumour related symptoms
22. History of active cancer during the past five years, except basal carcinoma of the skin or stage 0 cervical carcinoma

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> First randomisation:<br> Response rate (complete remission and 18-fluoro-2-deoxy-glucose-positron emission tomography [FDG-PET] negative partial remission or unconfirmed complete remission)<br><br> Second randomisation:<br> Failure free survival (measured from the date of second randomisation)<br><br> The protocol prescribes response evaluation during treatment after 4 and 8 cycles of R-CHOP and every 8 weeks during maintenance/observation. Thereafter follow up will be done every 6 months during the next 3 years and annually thereafter till 10 years after entry of the last patient. The total number of patients is expected to be recruited within 5 years. The analysis will be done approx 1 year after entry of the last patient.<br>

Secondary Outcome Measures

Name	Time	Method
<br> First randomisation:<br> 1. Failure free survival measured from the date of registration. Patients still alive or lost to follow up are censored at the last day they were known to be alive<br> 2. Overall survival measured from the time of registration<br> 3. Time to reach response<br> 4. Toxicity<br><br> Second randomisation:<br> 1. Overall survival<br> 2. Toxicity<br><br> The protocol prescribes response evaluation during treatment after 4 and 8 cycles of R-CHOP and every 8 weeks during maintenance/observation. Thereafter follow up will be done every 6 months during the next 3 years and annually thereafter till 10 years after entry of the last patient. The total number of patients is expected to be recruited within 5 years. The analysis will be done approx 1 year after entry of the last patient.<br>