Randomized phase III study of Rituximab with intensified CHOP chemotherapy versus Rituximab with High-Dose Sequential Therapy and Autologous Stem Cell Transplantation in Adult Patients (18-65 years) with Stage II-IV High-intermediate or High Risk DLBCL

ISRCTN	ISRCTN46136861
DOI	https://doi.org/10.1186/ISRCTN46136861
Protocol serial number	HO63
Sponsor	Dutch Haemato-oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON)
Funder	Amgen, Johnson & Johnson - Orthobiotech, Dutch Cancer Society, Novartis Pharma B.V., Roche Nederland BV

Submission date: 13/01/2006
Registration date: 13/01/2006
Last edited: 24/07/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr G.W. Imhoff, van
Scientific

University Medical Center Groningen
Department of Hematology
P.O. Box 30001
Groningen
9700 RB
Netherlands

Phone	+31 (0)50 3612354
Email	g.w.van.imhoff@int.umcg.nl

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	HOVON 63 NHL
Study objectives	The hypothesis to be tested is that the outcome in arm B is better than in arm A.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Non Hodgkin's lymphoma (NHL)
Intervention	Patients will be randomized between: Arm A: 6 cycles of rituximab-iCHOP every 2 weeks plus G-CSF: pegfilgrastim (Neulasta®) Arm B: 3 cycles of rituximab-iCHOP every 2 weeks plus G-CSF: pegfilgrastim (Neulasta®), followed by rituximab-HDT Induction I, rituximab-HDT Induction II plus daily G-CSF: filgrastim (Neupogen®, SingleJect®), followed by BEAM with ASCT. Daily G-CSF: filgrastim (Neupogen® SingleJect®) will replace pegfilgrastim in the iCHOP chemotherapy cycle during which stem cells will be harvested.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Rituximab, CHOP
Primary outcome measure(s)	Event-free survival i.e. time from registration to induction failure (less than PR after 3 x R-iCHOP, no CR [Cru] after 6 RiCHOP [arm A] or ASCT [arm B]), death, progression or relapse whichever occurs first; the time to failure of patients with induction failure (less than PR after 3 x R-iCHOP) is set at one day.
Key secondary outcome measure(s)	1. Complete response (including CRu) 2. Progression on protocol (progression or relapse after initial PR or CR during protocol treatment) 3. Overall survival measured form the time of registration 4. Disease-free interval (duration of the first CR) measured from the time of achievement of CR (including CRu) after protocol treatment to day of relapse or death from any cause (whichever occurs first)
Completion date	01/01/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	All
Target sample size at registration	250
Key inclusion criteria	1. Patients with a confirmed histologic diagnosis of DLBCL according to the WHO classification 2. Ann Arbor stage II-IV 3. High-intermediate or high risk NHL according to age-adjusted IPI score (aa IPI = 2-3) 4. DLBCL must be CD20 positive 5. Age 18-65 years inclusive 6. WHO performance status </= 2 7. Negative pregnancy test (if applicable) 8. Written informed consent
Key exclusion criteria	1. Intolerance of exogenous protein administration 2. Severe cardiac dysfunction (NYHA classification II-IV) or LVEF <45% 3. Significant renal dysfunction (serum creatinine >/= 150 mumol/l), unless related to NHL 4. Significant hepatic dysfunction (total bilirubin >/= 30 mumol/l or transaminases >/= 2.5 times normal level), unless related to NHL 5. Suspected or documented Central Nervous System involvement by NHL 6. Testicular DLBCL 7. Primary mediastinal B cell lymphoma 8. Patients known to be HIV-positive 9. Patients with active, uncontrolled infections 10. Patients with uncontrolled asthma or allergy, requiring steroid treatment 11. Patient is a lactating woman 12. Unwillingness or not capable to use effective means of contraconception (all men and pre-menopausal women) 13. 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 14. History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
Date of first enrolment	28/10/2005
Date of final enrolment	01/01/2009

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Center Groningen

Groningen
9700 RB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan