Clinical picture: NHL (Non Hodgkin Lymphoma)

Trial: HOVON 84 NHL

News

HO84 news

1. Overview

Summary

Randomized phase III study on the effect of early intensification of rituximab in combination with 2-weekly CHOP chemotherapy followed by rituximab maintenance in patients with diffuse large B-cell lymphoma

Status

closed

Study details

Type of study

Prospective randomized Phase III study

Type of monitoring for this study

Site evaluation visits

Target number of patients

600

Current number of patients

585

Date of activation

25-Oct-2007

Approved by

EudraCTnr.: 2006-005174-42
CKTO: 2006-14, 08 February 2007
MEC: METC Erasmus MC 2007-055, 25 May 2007

Change history / amendement

Amendment 1 approved by METC Erasmus MC, 16 September 2009
Amendment 5 (Addendum Pharmacokinetic Evaluation Rituximab) approved by METC Erasmus MC, 30 August 2011

Study objectives

To evaluate the efficacy of:
a. early intensification of rituximab combined with 2- weekly CHOP+G-CSF (R-CHOP14) in remission induction treatment in comparison to standard RCHOP14
b. maintenance treatment with rituximab in patients in remission after R-CHOP14 in comparison to no further treatment

2. Patient eligibility criteria

Inclusion criteria

Patients with a confirmed histologic diagnosis of diffuse large B-cell lymphoma (DLBCL) based upon a representative histology specimen according to the WHO classification (see appendix A)
DLBCL must be CD20 positive
Ann Arbor stages II-IV (see appendix C)
Age 18-65 (inclusive) years and aa-IPI 1-3 (see appedix G)
OR Age 66-80 (inclusive) years and aa-IPI 0-3 (see appendix G)
WHO performance status 0 - 2 (see appendix E)
Written informed consent


Eligibility criteria for second randomization: Patients achieving a CR (or FDG-PET negative PR/CRu) after 6 cycles (elderly patients) or 8 cycles (young patients) of R-CHOP14 will be randomized to maintenance treatment with rituximab or no further treatment.
Patients in complete remission or FDG-PET negative partial remission/unconfirmed complete remission at least 4 weeks after the last cycle of R-CHOP14 (including last rituximab administration)
Time interval since last cycle of R-CHOP14 (including last rituximab administration) between 4 and 8 weeks
No rituximab-related adverse event necessitating stopping of rituximab administration
No active infection
Written informed consent

Exclusion criteria

Age 18-65 (inclusive) years and aa-IPI 0 (no risk factors, see appendix G)
Intolerance of exogenous protein administration
Severe cardiac dysfunction (NYHA classification III-IV, see appendix F) or LVEF < 45% Congestive heart failure or symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication. Myocardial infarction during the last 6 months
Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value) unless clearly related to NHL involvement
Patients with uncontrolled asthma or allergy, requiring systemic steroid treatment
Significant hepatic dysfunction (total bilirubin ≥ 30µmol/l or transaminases ≥ 2.5 x upper normal limit), unless related to NHL
Significant renal dysfunction (serum creatinine ≥ 150 umol/l or clearance ≤ 60 ml/min), unless related to NHL
Clinical signs of severe cerebral dysfunction
Suspected or documented Central Nervous System involvement by NHL
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
Testicular DLBCL
Primary mediastinal B cell lymphoma
Transformed indolent lymphoma
(EBV) post-transplant lymphoproliferative disorder
Secondary lymphoma after previous chemotherapy or radiotherapy
Major surgery, other than diagnostic surgery, within the last 4 weeks
Patients with active uncontrolled infections
Patients known to be HIV-positive
Active chronic hepatitis B or C infection
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)
Life expectancy < 6 months
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
History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma

3. Registration (& randomization) of patients

Registration

Central registration at the HOVON Data Center:
Erasmus MC Cancer Institute, Clinical Trial Center (Hs-423)
P.O. Box 2040
NL-3000 CA Rotterdam
Phone number.: +31.10.7041560 (working days 9.00-17.00)
Fax number.....: +31.10.7041028
TOP address...: http://www.hdc.hovon.nl/top

Registration criteria

Protocol number
Institution name
Name of caller/responsible investigator
Patient's initials or code
Patient's hospital record number (optional)
Sex
Date of birth
Age-adjusted IPI risk score
PA number
Original PA laboratory (pathologist and institution)
Eligibility criteria

4. Participating parties

Principal Investigator(s)

Mw. Dr. P.J. Lugtenburg (Erasmus MC - Centrum)

Co-Investigator(s)

Mw. J.M. Zijlstra-Baalbergen (VUMC)

Statistician(s)

Dr. W. Ghidey Alemayehu (Erasmus MC - Daniel)
Dhr. Dr. B. van der Holt (Erasmus MC - Daniel)

Other functions

Central Coordinator - Special Investigations - Dhr. Dr. E.F.I. Comans (VUMC)
Central Coordinator - Special Investigations - Prof. Dr. W.J.G. Oyen (Radboudumc)
Central Coordinator - Special Investigations - Dr. J. Pruim (UMCG)
Reviewer - Imaging - Mw. C. Karga (VUMC)
Reviewer - Pathology - Prof. Dr. Ph.M. Kluin (UMCG)
Reviewer - Pathology - Dhr. Dr. K.H. Lam (Erasmus MC - Centrum)
Reviewer - Pathology - Dhr. Dr. J.J. Oudejans (Diakonessenhuis)

Central data management

Nicole Thuss (n.thuss@erasmusmc.nl)
Henk Hofwegen (h.hofwegen@erasmus.mc.nl)
Tamara van Dijk (t.m.r.vandijk@erasmusmc.nl)
Christel van Hooije (c.vanhooije@erasmusmc.nl)

5. Participating sites

6. Instruction videos

7. Download documentation / forms

 Protocol