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Clinical picture: CLL (Chronical Lymfatic Leukemia)

Trial: HOVON 141 CLL

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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HO141 news

20 Apr 2020: The updated pharmacy info letter V4 has been uploaded and can be found on the HOVON website.


For Dutch sites only, a new biobank protocol and ICF has been implemented. The documents have been sent out to sites and can be found on the HOVON website. Further, tubes for additional blood samples have been sent to sites.


20MAR2019: Amendment 02 has been approved in the Netherlands.

The most important change is that the criterion for randomization after cycle 15 has been changed from ‘MRD negativity after cycle 12 (PB) AND at day 15 cycle 15 (PB and BM)’ to ‘MRD negativity at day 15 of cycle 15 (PB and BM)’. The randomization form has not been updated.

New documents:

-          HO141_protocol-V04_20DEC2018



23JAN2019: The study is closed for inclusion of new patients.



08NOV2018: Amendment 01 has been approved.


New documents:

- HO141_protocol_AM01_V3_25JUL2018

- HO141_ICF_NL_v3_18JUL2018

- HO141_REGRAND_17OCT2018

- HO141 Pharmacy info letter_01NOV2018

- 20181009_HOVON141 Lab manual_1.8 - HOVON Sites –Final


20JUL2017: The study has been approved by EC, CA and the Biobank Committee in the Netherlands. All sites have been informed and may start with the local submission.


10JUL2017: The study has been approved in Denmark and the first site will open shortly.

The Netherlands is still awaiting approval from the Biobank Committee. As soon as we receive approval, the ITF will be sent to the sites.

1. Overview


A prospective, multicenter, phase-II trial of ibrutinib plus venetoclax in physically fit (CIRS ≤ 6) and unfit (CIRS > 6) patients with creatinine clearance ≥ 30 ml/min who have relapsed or refractory chronic lymphocytic leukemia (RR-CLL) with or without TP53 aberrations




HOVON, Nordic CLL Group

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.

 Patienten informatie

Study details

Type of study

Prospective randomized Phase II study

Echelon level

Level D

Type of monitoring for this study

Site evaluation visits

Target number of patients


Current number of patients


Date of activation


Study objectives

The primary objective:
Evaluate efficacy of ibrutinib + venetoclax (VI) in terms of progression free survival (PFS, reinitiated treatment not considered progression) 12 months after stopping treatment for patients achieving MRD negativity at 12 and 15 months in previously treated patients with CLL.

Secondary objectives:
Evaluation of the efficacy in terms of MRD at 12 months after stopping treatment (month 27)
Evalution of efficacy in terms of PFS (IWCLL criteria)
number of patients reinitiating treatment, time to treatment failure after reinitiated treatment, time to next treatment, MRD month 12 (PB) and 15 (PB and BM) and at later time points in PB, QoL, OS, CR/PR/SD at month 3, 9, 12, 15, 27 and end of study
– all secondary endpoints for patients MRD negative randomized to stopping treatment at 15 months, patients randomized to ibrutinib maintenance and patients MRD positive at month 12/15 continuing on ibrutinib maintenance.
– To evaluatie safety with regards to type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment.
– To evaluate patient related outcomes, measured in terms of health-related quality of life by EORTC QLQ-C30 and QLQ-CLL17 questionnaires.

2. Patient eligibility criteria

Inclusion criteria

♦ Documented relapsed/refractory CLL or SLL requiring treatment according to IWCLL criteria
(no limits on previous treatment lines; CD20 and steroids are not considered prior therapy
♦ Age at least 18 years.
♦ Adequate bone marrow function defined as:
Absolute neutrophil count (ANC) >0.75 x 109/L
Platelet count >30,000 /μL 30 x 109/L.
Hemoglobin >8.0 g/dL (5 mmol/L)
Unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow
♦ Creatinine clearance (CrCL) ≥ 30ml/min calculated according to the modified formula of
Cockcroft and Gault or directly measured with 24hr urine collection.
♦ Adequate liver function as indicated
Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper
limit of normal (ULN)
Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic
Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and PTT
(activated partial thromboplastin time [aPTT]) <1.5 x ULN (unless abnormalities are
related to coagulopathy or bleeding disorder).
♦ Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients
positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is
performed every month until 12 months after last dose), negative testing for hepatitis C RNA
within 42 days prior to registration.
♦ WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL.
♦ Negative pregnancy test at study entry (for women of childbearing potential).
♦ Male and female subjects of reproductive potential must agree to use both a highly effective
method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence , or sterilized partner) and a barrier method
(e.g., condoms, cervical ring, sponge, etc.) during the period of therapy and for 90 days after
the last dose of study drug.
♦ Ability and willingness to provide written informed consent and to adhere to the study visit
schedule and other protocol requirements.
♦ Written informed consent.

Exclusion criteria

Any prior therapy with ibrutinib and/or venetoclax.
Transformation of CLL (Richter’s transformation).
Patients with a history of confirmed PML.
Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment.
Known allergy to xanthine oxidase inhibitors and/or rasburicase.
Known bleeding disorders (eg, von Willebrand’s disease or hemophilia).
Uncontrolled or active infection.
Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see Appendix X).
or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists.
Please note: Patients being treated with NOACs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib.
History of stroke or intracranial hemorrhage within 6 months prior to randomization.
Major surgery within 4 weeks of first dose of study drug.
Use of investigational agents which might interfere with the study drug within 28 days prior to registration.
Vaccination with live vaccines within 28 days prior to registration
Pregnant women and nursing mothers.
Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

3. Registration (& randomization) of patients


Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:
Trial Online Process (TOP, A logon to TOP can be requested at the HOVON Data Center for participants.
By faxing the completed registration/randomization CRF +31.10.7041028 Monday through Friday, from 09:00 to 17:00 CET
By phone +31.10.7041560 Monday through Friday, from 09:00 to 17:00 CET

Registration criteria

The following information will be requested:

♦ Protocol number
♦ Institution name
♦ Name of caller/responsible investigator
♦ Local patient code (optional)
♦ Sex
♦ Year of birth
♦ Date written informed consent
♦ Specific items patient gives consent for (see ICF)
♦ Eligibility criteria

4. Participating parties

Principal Investigator(s)

Prof. Dr. A.P. Kater (AMC)


Mw. Dr. S. Kersting (Hagaziekenhuis, locatie Leyweg)
Dhr. Dr. M.D. Levin (A. Schweitzer ZH, Dordwijk)

Coordinating Investigator(s)

Dr. M. Mattsson (Uppsala Akademiska Sjukhuset)
Dr. C. Niemann (Rigshospitalet Copenhagen)
M.D. J. Ranti (Turku University Central Hospital)
Dr. T. Salmi (Turku University Central Hospital)
Dr. H.T.T. Tran (Akershus University Hospital)


Dhr. K. Nasserinejad (Erasmus MC)

Monitor - Site Evaluation Visits

MonitorTeamHDC (Erasmus MC - Daniel)

Other functions

Central Coordinator - MRD - CLLlabAmsterdam (AMC)
Central Coordinator - MRD - CLLlabCopenhagen (Rigshospitalet Copenhagen)
Central Coordinator - MRD - Dhr. J. Dobber (AMC)
Central Coordinator - MRD - Mrs. J. Dubois (AMC)
Central Coordinator - MRD - Ms. B. Gall (Rigshospitalet Copenhagen)
Central Coordinator - MRD - Ms. T. Hahn Enevoldsen (Rigshospitalet Copenhagen)
Central Coordinator - MRD - Dhr. Dr. C.H.M. Mellink (AMC)
Central Coordinator - MRD - Trialbureau Hematologie AMC (AMC)


K. Nasserinejad (

Trial manager

W. Razawy (

Central data management

Rene Hollestein (

5. Participating sites

Included patients *
BE-Antwerpen-ZNA Stuivenberg
BE-Brugge-Algemeen Ziekenhuis St. Jan
BE-Bruxelles-Cliniques Universitaires St. Luc
BE-Haine-Saint-Paul-Hopital de Jolimont
BE-Leuven-UZ Gasthuisberg
DK-Aalborg-Aalborg Hospital
DK-Copenhagen-Rigshospitalet Copenhagen
DK-Herlev-Herlev Hospital
DK-Holstebro-Regionshospital Holstebro
DK-Odense-Odense Universitetshospital
Show 36 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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