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Clinical picture: NHL (Non Hodgkin Lymphoma)


1. Overview
Study details
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms

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HO133 News

18APR2018: Study documents regarding AM1 are uploaded on the HOVON website.


18OCT2017: The first site in Belgium is opened for patient inclusion.

10OCT2017: The first site in the Netherlands opened for patient inclusion.


26JUL2017: HOVON Lymphoma working group has decided to implement the rituximab maintenance. Therefore, all Dutch HOVON sites should implement the maintenance (every 2 months up to 3 years) to all three study arms. Belgian sites will follow once the national reimbursement for rituximab is possible. Please also see the sent newsletters in the study documentation.


11JAN2017: Start Up meeting for participating HOVON sites was held in Utrecht.


18SEP2015: Participants Inquiry is sent to all HOVON sites. Planning is that study will first start in Germany (Q4 2015) after which HOVON will join with 25-30 sites in NL+BE.


1. Overview


Randomized, three-arm, parallel-group, open label, international phase III trial comparing six alternating courses of R-CHOP/R-DHAP (one cycle every 21 days) followed by ASCT versus the combination with ibrutinib in induction and maintenance (2 years) or the experimental arm without ASCT.




Participating Groups: GLSG (sponsor), HOVON, Nordic Lymphoma Group, FIL, SAKK, PLRG, GELTAMO, NCRI

Uitleg patienten informatie

Beste patient, hieronder vindt u een link naar de patienten informatie die beschikbaar is voor deze studie. Mochten er vragen zijn, dan kunt u deze het beste stellen aan uw behandelend arts.

Beste patiënt, hieronder vindt u een link naar de patiënten informatie die beschikbaar is voor deze studie. Mochten er vragen zijn, dan kunt u deze het beste stellen aan uw behandelend arts.

 Patienten informatie

Study details

Type of study

Prospective randomized Phase III study

Echelon level

Level D

Echelon level specification

Agreements should be made with a higher echelon site for study parts that your center cannot execute.

Type of monitoring for this study

Study specific

Target number of patients


Current number of patients


Date of first EC&CA submission


Date of activation


Approved by

EudraCTnr.: 2014-001363-12

Dutch central EC: 28Jul2017
Dutch CA: 18Apr2017

Belgian central EC: 29Jun2017
Belgian CA: 24Apr2017

Study objectives

Primary Objective:
To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance (experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance (experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS).

Secondary Objectives:
To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints
To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints

Exploratory Objectives:
To compare feasibility of ASCT in arm A+I vs. arm A
To compare minimal residual disease status between the three treatment groups
To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status
To determine the prognostic value of minimal residual disease status
To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose
To determine clinical and biological prognostic and predictive factors
To determine the role of total body irradiation (TBI) in ASCT conditioning

2. Patient eligibility criteria

Inclusion criteria

All patients must meet the following criteria:
Histologically confirmed diagnosis of MCL according to WHO classification
suitable for high-dose treatment including high-dose Ara-C
Stage II-IV (Ann Arbor)
Age ≥ 18 years and ≤ 65 years
Previously untreated MCL
At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
ECOG/WHO performance status ≤ 2
The following laboratory values at screening (unless related to MCL):
 - Absolute neutrophil count (ANC) ≥ 1000 cells/uL
 - Platelets ≥ 100,000 cells/uL
 - Transaminases (AST and ALT) ≤ 3 x upper limit of normal (ULN)
 - Total bilirubin ≤ 2 x ULN unless due to known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
 - Creatinine ≤ 2 mg/dL or calculated creatinine clearance ≥ 50 mL/min
Written informed consent form according to ICH/EU GCP and national regulations
Sexually active men and women of child-bearing potential must agree to use one of the highly effective contraceptive methods (combined oral contraceptives using two hormones, contraceptive implants, injectables, , intrauterine devices, sterilized partner) together with one of the barrier methods (latex condoms, diaphragms, contraceptive caps) while on study; this should be maintained for 90 days after the last dose of study drug

Exclusion criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study.

Major surgery within 4 weeks prior to randomization.
Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg phenprocoumon).
History of stroke or intracranial hemorrhage within 6 months prior to randomization.
Requires treatment with strong CYP3A4/5 inhibitors.
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.
Known CNS involvement of MCL
Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of ibrutinib itself or to the excipients in its formulation)
Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon except prephase therapy outlined in this trial protocol
Serious concomitant disease interfering with a regular therapy according to the study protocol:
 - Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN )
 - Pulmonary (chronic lung disease with hypoxemia)
 - Endocrinological (severe, not sufficiently controlled diabetes mellitus)
 - Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinin clearance < 50 ml/min)
 - Impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl unless due to morbus Meulengracht (Gilbert-Meulengracht-Syndrome)
Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test)
Prior organ, bone marrow or peripheral blood stem cell transplantation
Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer or in situ uterine cervix cancer
Pregnancy or lactation
Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
Subjects not able to give consent
Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial
Participation in another clinical trial within 30 days before randomization in this study.

3. Registration (& randomization) of patients


Via eCRF system of sponsor KU Munich:

4. Participating parties

Principal Investigator(s)

Prof. Dr. M. Dreyling (Klinikum der Universität München)

Coordinating Investigator(s)

Mw. Dr. J.K. Doorduijn (Erasmus MC)
Prof. Dr. G.E.G. Verhoef (UZ Gasthuisberg)


Ms. Dr. E. Hoster (Klinikum der Universität München)

Central Data Manager(s)

Dr. M. Unterhalt (University Hospital Grosshadern)

Monitor - Study Specific

MonitorTeamHDC (Erasmus MC - Daniel)

Other functions

Central Coordinator - MRD - Mw. C. Homburg (Sanquin Research)
Central Coordinator - MRD - Dhr. Dr. V.H.J. van der Velden (Erasmus MC)

Trial manager

mw. N. Thuss (

Central data management

Will be done by sponsor KU München.
eCRF system:

Other functions

Please contact monitors at

5. Participating sites

Included patients *
BE-Antwerpen-ZNA Stuivenberg
BE-Antwerpen Edegem-Universitair Ziekenhuis Antwerpen
BE-Brugge-Algemeen Ziekenhuis St. Jan
BE-Brussel-Universitair Ziekenhuis Brussel
BE-Gent-UZ Gent
BE-Haine-Saint-Paul-Hopital de Jolimont
BE-Leuven-UZ Gasthuisberg
Show 22 more...
* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos

7. Download documentation / forms

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