ISRCTN - ISRCTN82286322: 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

Plain English Summary

Not provided at time of registration

Trial website

http://www.hovon.nl

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 type

Research organisation

Website