Contact information
Type
Scientific
Primary contact
Dr P.J. Lugtenburg
ORCID ID
Contact details
Erasmus Medical Centre
Afd. Hematologie
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
+31 (0)10 463 3123
p.lugtenburg@erasmusmc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HO84
Study information
Scientific title
Acronym
HOVON 84 NHL
Study hypothesis
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
Ethics approval was received from the METC of the Erasmus Medical Center in Rotterdam (The Netherlands) on the 25th May 2007 (ref: 2007-055).
Study design
Multicentre, randomised, active controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
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 trial start date
01/08/2007
Overall trial end date
31/03/2012
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Senior
Gender
Not Specified
Target number of participants
550
Participant 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
Recruitment start date
01/08/2007
Recruitment end date
31/03/2012
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Centre
Rotterdam
3000 CA
Netherlands
Sponsor information
Organisation
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands) - Data Centre
Sponsor details
Erasmus Medical Centre
Daniel den Hoed Kliniek
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
+31 (0)10 439 1568
hdc@erasmusmc.nl
Sponsor type
Research organisation
Website
Funders
Funder type
Industry
Funder name
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.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list