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
| ISRCTN | ISRCTN82286322 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82286322 |
| Secondary identifying numbers | HO84 |
- Submission date
- 23/08/2007
- Registration date
- 23/08/2007
- Last edited
- 07/10/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr P.J. Lugtenburg
Scientific
Scientific
Erasmus Medical Centre
Afd. Hematologie
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
| Phone | +31 (0)10 463 3123 |
|---|---|
| p.lugtenburg@erasmusmc.nl |
Study information
| Study design | Multicentre randomised active-controlled parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | 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 |
| Study acronym | HOVON 84 NHL |
| Study objectives | First randomisation: The hypothesis to be tested is that the outcome in arm B (early intensification of rituximab combined with two weekly CHOP) is better than in arm A (no intensification of rituximab). Second randomisation: The hypothesis to be tested is that the outcome in arm 2 (maintenance treatment with Rituximab) is better than in arm 1 (no further treatment). |
| Ethics approval(s) | Approved 25/05/2007, the METC of the Erasmus Medical Center in Rotterdam (Netherlands), ref: 2007-055 |
| Health condition(s) or problem(s) studied | Diffuse large B-cell lymphoma |
| Intervention | Arm A: eight cycles of rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP14) plus Granulocyte Colony-Stimulating Factor (G-CSF) pegfilgrastim (Neulasta) Arm B: eight cycles of R-CHOP14 plus G-CSF pegfilgrastim (Neulasta) with intensification of rituximab (MabThera) during the first four cycles Arm 1: no further treatment Arm 2: maintenance treatment with rituximab (MabThera) once every eight weeks until relapse (for a maximum period of 24 months) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) |
| Primary outcome measure | First randomisation: Response rate (complete remission and 18-fluoro-2-deoxy-glucose-positron emission tomography [FDG-PET] negative partial remission or unconfirmed complete remission) Second randomisation: Failure free survival (measured from the date of second randomisation) 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. |
| Secondary outcome measures | First randomisation: 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 2. Overall survival measured from the time of registration 3. Time to reach response 4. Toxicity Second randomisation: 1. Overall survival 2. Toxicity 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. |
| Overall study start date | 01/08/2007 |
| Completion date | 31/03/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Both |
| Target number of participants | 550 |
| Total final enrolment | 600 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/08/2007 |
| Date of final enrolment | 31/03/2012 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Erasmus Medical Centre
Rotterdam
3000 CA
Netherlands
3000 CA
Netherlands
Sponsor information
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands) - Data Centre
Research organisation
Research organisation
Erasmus Medical Centre
Daniel den Hoed Kliniek
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
| Phone | +31 (0)10 439 1568 |
|---|---|
| hdc@erasmusmc.nl | |
| Website | http://www.hovon.nl |
"ROR" |
https://ror.org/056kpdx27 |
Funders
Funder type
Industry
HOVON receives unrestricted grants and/or financial support from Amgen, Johnson & Johnson-Orthobiotech, Roche and Novartis for the execution of investigator sponsored trials. In addition HOVON is supported by the Dutch Cancer Society.
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 30/07/2020 | 07/10/2021 | Yes | No |
Editorial Notes
07/10/2021: Publication reference and total final enrolment added.
