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Clinical picture: CLL (Chronical Lymfatic Leukemia)

Trial: HOVON 140 CLL


News
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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News


HO140 news

11DEC2017_Amendment 3 is approved for BE. It mainly concerns the update of the protocol (3.0) and Mabthera will be provided as study medication for the FCR/BR arm as well. You can best download the HO140_ITF_BE_11DEC2017.zip file (found at section "Belgium specific documentation"). In the HO140_ITF overview folders en files_be_11dec2017.xls is stated which document is located at which directory and also indicates which documents are removed / added.

 

05DEC2017_Central lab shipment forms updated. The TNT Express hotline number on the central lab shipment forms were adjusted. Please work closely with the Clinical Desk of TNT, so the arrival of the samples will not be delayed. The new version was send to the sites and placed on the HOVON website and the ITF.

 

13NOV2017_Lab manual updated. Use the Clinical Desk of TNT to send samples to the central lab. Do not use the waybills send by GCLLSG, the clinical desk of TNT will create those for you. Find further information in the lab manual.

  

08NOV2017_CRF guidelines added. There were previously some minimal guidelines on how to fill out the CRFs. These are now renewed. you can find them after logging in, at CRF instructions.

 

25OCT2017_Amendment 3 is approved for NL. It mainly concerns the update of the protocol (3.0) and Mabthera will be provided as study medication for the FCR/BR arm as well. You can best download the HO140_ITF_NL_25OCT2017.zip file (found at section "other documents"). In the HO140_ITF_25OCT2017_Overview folders & files.xlsx is stated which document is located at which directory and also indicates which documents are removed / added.

 

20SEP2017_Correction of QoL (QLQ-C30) Dutch version. By accident the version previously provided to the Dutch sites was still carrying the complete birthdate. The new version was send to the sites today and placed on the HOVON website and the ITF.

 

12SEP2017_Amendment 2 + 3 submission available for BE. The local submission of amendment 02 and amendment 03 are now available for Belgium as download of a zip file in section "Belgian specific documentation". PLease submit both dossiers to your local EC.

 

12SEP2017_Amendment 2 is approved for NL. It mainly concerns the update of the protocol and trial medication documents like Venetoclax patient diary, card and SPC. You can best download the HO140_ITF_NL_12SEP2017.zip file (found at section "other documents").  In the HO140_ITF_12SEP2017_Overview folders & files.xlsx is stated which document is located at which directory and also indicates which documents are removed / added.

 

Please note that you can find all participating sites and whether or not they are activated in the section Registration & randomization of patients.

 

08MAY2017_Amendment 1 is approved for NL. It mainly concerns an update of the ICF (now version 13MAR2017). Please send in this version when you wish to get activated.

 

02MAR2017_Study has been opened recently. You can best download the HO140_ITF_02MAR2017.ZIP file to have all documents at once. In the HO140_ITF_02MAR2017_Overview folders & files.xlsx is stated which document is located at which directory. Please let me know if there are any questions (p.cornelisse@erasmusmc.nl)

 


1. Overview



Summary

A phase 3 multicenter, randomized, prospective, open-label trial of standard chemoimmunotherapy (FCR/BR) versus rituximab plus venetoclax (RVe) versus obinutuzumab (GA101) plus venetoclax (GVe) versus obinutuzumab plus ibrutunib plus venetoclax (GIVe) in fit patients with previously untreated chronic lymphocytic leukemia (CLL) without del (17p) or TP53 mutation.


Status

open


Members

GCLLSG sponsor. HOVON, SAKK, Nordic CLL group



Study details



Type of study

Prospective randomized Phase III study


Echelon level

Level D


Type of monitoring for this study

Study specific


Target number of patients

920


Current number of patients

0


Date of first EC&CA submission

16-Feb-2017


Date of activation

02-Mar-2017


Approved by

NL EC: 06FEB2017
BE EC: 31MAR2017
NL CA: 19DEC2016
BE CA: 26JAN2017


Study objectives

The primary objective of the study is to evaluate the efficacy of obinutuzumab (GA101) plus venetoclax (GVe) versus standard chemoimmunotherapy (BR/FCR) [concerning MRD negativity meas-ured by flow cytometry in peripheral blood (PB) at month 15] and obinutuzumab plus ibrutinib plus venetoclax (GIVe) versus standard chemoimmunotherapy (BR/FCR) [concerning progression free survival (PFS)] in previously untreated, fit CLL patients without del(17p) or TP53 mutation.

Secondary objectives of the study are the evaluation of the efficacy of rituximab plus venetoclax (RVe) versus standard chemoimmunotherapy (BR/FCR), GVe and GIVe [concerning MRD negativity measured by flow cytometry in PB at month 15 and PFS].


2. Patient eligibility criteria



Inclusion criteria

Documented CLL requiring treatment according to iwCLL criteria.
Age at least 18 years.
Life expectancy ≥ 6 months.
Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
Adequate bone marrow function indicated by a platelet count >30 x10^9/L (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy)
Creatinine clearance ≥70ml/min calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85) or directly measured with 24hr urine collection. For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 70
ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min.
Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome.
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 treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration.
Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.


Exclusion criteria

Any prior CLL-specific therapies (except corticosteroid treatment administered
due to necessary immediate intervention; within the last 10
days before start of study treatment, only dose equivalents of 20 mg
prednisolone are permitted).
Transformation of CLL (Richter transformation).
Decompensated hemolysis, defined as ongoing hemoglobin drop in
spite of three more concurrent treatments being administered for hemolysis
Detected del(17p) or TP53 mutation.
Patients with a history of PML.
Any comorbidity or organ system impairment rated with a single CIRS
(cumulative illness rating scale) score of 4 (excluding the
eyes/ears/nose/throat/larynx organ system), a total CIRS score of
more than 6 or any other life-threatening illness, medical condition or
organ system dysfunction that, in the investigator´s opinion, could
comprise the patients safety or interfere with the absorption or metabolism
of the study drugs (e.g, inability to swallow tablets or impaired
resorption in the gastrointestinal tract).
Urinary outflow obstruction.
Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention before (unless the malignant
disease is in a stable remission due to the discretion of the treating
physician) or showing signs of progression after curative treatment.
Uncontrolled or active infection.
Patients with known infection with human immunodeficiency virus
(HIV).
Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/
inducers.
Anticoagulant therapy with warfarin or phenoprocoumon,
(rotation to alternative anticoagulation is allowed, but note that patients
being treated with NOAKs 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
registration.
Use of investigational agents which might interfere with the study
drug within 28 days prior to registration.
Vaccination with live vaccines 28 days prior to registration.
Major surgery less than 30 days before start of treatment.
History of severe allergic or anaphylactic reactions to humanized or
murine monoclonal antibodies, known sensitivity or allergy to murine
products.
Known hypersensitivity to any active substance or to any of the excipients
of one of the drugs used in the trial.
Pregnant women and nursing mothers (a negative pregnancy test is
required for all women of childbearing potential within 7 days before
start of treatment; further pregnancy testing will be performed regularly).
Fertile men or women of childbearing potential unless: a. surgically sterile or ≥ 2 years after the onset of menopause
b. willing to use two methods of reliable contraception including one
highly effective contraceptive method (Pearl Index <1) and one
additional effective (barrier) method during study treatment and
for 18 months after the end of study treatment.
Legal incapacity.
Prisoners or subjects who are institutionalized by regulatory or court
order.
Persons who are in dependence to the sponsor or an investigator.


3. Registration (& randomization) of patients



Registration

Goes through IVRS system of GCLLSG.

Inclusion rates globally and for BE and NL seperatly will be uploaded at the first monday of the month

Country PI Name City PatCount
AT Vejle Torben Plesner 1
AT Wien Daniel Heintel 2
AT Wien Ulrich Jäger 4
BE Antwerpen Ka Lung Wu 3
BE Leuven A.M.H. Janssen 4
BE Roeselare Dries Deeren 1
CH Basel Dominik Heim 1
CH Bellinzona Davide Rossi 1
CH Liestal G. Favre 3
CH Münsterlingen Rudolf Benz 1
CH St. Gallen Michael Baumann 5
CH Winterthur Jeroen Goede 1
CH Zürich Adrian Schmidt 1
DE Amberg Ludwig Fischer von Weikersthal 1
DE Bonn Walter Verbeek 1
DE Bremen Ralf Ulrich Trappe 1
DE Cologne Barbara Eichhorst 7
DE Dortmund Clemens Schulte 4
DE Dresden Johannes Schetelig 1
DE Dresden Thomas Illmer 7
DE Eschweiler Peter Staib 2
DE Essen Christiane Kuhnert 2
DE Freiburg Rainer Claus 4
DE Goslar Mark-Oliver Zahn 1
DE Hamburg Thomas Wolff 1
DE Hannover Michael Königsmann 1
DE Kassel Ulrike Soeling 4
DE Kiel Matthias Ritgen 1
DE Koblenz Christoph van Roye 2
DE Landshut Ursula Vehling-Kaiser 1
DE Lebach Stephan Kremers 1
DE Leer Lothar Müller 2
DE Magdeburg Kathleen Jentsch-Ulrich 1
DE Mainz Georg Hess 1
DE Mannheim Manfred Hensel 1
DE Mayen Maria Theresia Keller 1
DE Mönchengladbach Ulrich Graeven 4
DE München Christian Bogner 1
DE München Clemens Wendtner 1
DE München Till Seiler 2
DE Mutlangen Holger Hebart 5
DE Paderborn Tobias Gaska 7
DE Ravensburg Thomas Decker 1
DE Regensburg Alexander Kroeber 2
DE Rostock Sebastian Böttcher 2
DE Siegburg Stefan Fronhoffs 1
DE Stuttgart Matthias Vöhringer 2
DE Ulm Stephan Stilgenbauer 5
DE Würzburg Björn Schöttker 8
DK Aalborg Ilse Christiansen 3
DK Herlev Lisbeth Enggaard 3
DK Kopenhagen Carsten Utoft Niemann 11
DK Odense Henrik Frederiksen 2
DK Roskilde C.B. Poulsen 3
FI Turku Tommi Salmi 2
IE Dublin Patrick Thornton 1
IE St. James Hospital Elisabeth Vandenberghe 3
IE University Hospital Waterford Ezzat Elhassadi 1
NL Amersfoort J.C.Regelink 2
NL Amsterdam A.P. Kater 5
NL Amsterdam M. Chamuleau 1
NL Breda M. van der Klift 4
NL Dordrecht M.D. Levin 1
NL Ede S. Wittebol 1
NL Leuwarden M. Hoogendoorn 1
NL Nieuwegein H.R.Koene 1
NL Rotterdam M.B.L. Leys 1
NL s-Hertogenbosch D.E. Issa 4
NL Zwolle E. C. Dompeling 2
SE Falun Max Flogegard 1
SE Linköping Kourosh Lotfi 2
SE Lulea Brigitta Lauri 2
SE Lund Gunnar Juliusson 3
SE Uppsala Matthias Mattson 1


-------------------------------------------------------------------
Dutch and Belgium site numbers:

BE - Antwerpen - ZNA ___nr: 2394 ACTIVATED
BE - Brugge - St. Jan zkh ___nr: 721 ACTIVATED
BE - Brussel - St. Luc ___nr: 743
BE - Leuven - UZ Gasthuisberg ___nr: 736 ACTIVATED
BE - Roeselare - AZ Delta ___nr: 2396 ACTIVATED
BE - Yper - Jan Yperman zkh ___nr: 2407 ACTIVATED
NL - Alkmaar - Noordwest zkh Groep ___nr: 2404
NL - Amersfoort - Meander MC ___nr: 1765 ACTIVATED
NL - Amsterdam - AMC ___nr: 1767 ACTIVATED
NL - Amsterdam - VUMC ___nr: 1769 ACTIVATED
NL - Arnhem - Rijnstate ___nr: 2405
NL - Breda - Amphia ___nr: 2406 ACTIVATED
NL - Cappelle ad Ijsel - IJsselland zkh ___nr: 1771 ACTIVATED
NL - Delft - RdGG ___nr: 1456
NL - Den Bosch - JBZ ___nr: 2381 ACTIVATED
NL - Deventer - Deventer zkh ___nr: 2397
NL - Dordrecht - ASZ ___nr: 1774 ACTIVATED
NL - Ede - Gelderse Vallei ___nr: 2382 ACTIVATED
NL - Eindhoven - MMC ___nr: 1933 ACTIVATED
NL - Enschede - MST ___nr: 1356
NL - Gouda - Groene Hart zkh ___nr: 2383 ACTIVATED
NL - Groningen - UMCG ___nr: 1777
NL - Hengelo - ZGT ___nr: 2427
NL - Hoofddorp - Spaarne Gasthuis ___nr: 2398 ACTIVATED
NL - Leeuwarden - MCL ___nr: 1494 ACTIVATED
NL - Leiden - LUMC ___nr: 2399
NL - Maastricht - MUMC ___nr: 2400
NL - Nieuwegein - St. Antonius zkh ___nr: 1357 ACTIVATED
NL - Nijmegen - CWZ ___nr: 2403 ACTIVATED
NL - Nijmegen - Radboud UMC ___nr: 2385 ACTIVATED
NL - Rotterdam - Maasstad zkh ___nr: 1808 ACTIVATED
NL - Sneek - Antonius zkh ___nr: 2401 ACTIVATED
NL - Terneuzen - ZorgSaam zkh ___nr: 1807 ACTIVATED
NL - Tilburg - ETZ ___nr: 2402 ACTIVATED
NL - Utrecht - UMCU ___nr: 2386
NL - Venlo - VieCuri MC ___nr: 2387 ACTIVATED
NL - Zaandam - Zaans MC ___nr: 2388
NL - Zwolle - Isala ___nr: 1358 ACTIVATED


Registration criteria

The following information will be requested:



protocol number
institution name
name caller/responsible investigator
sex
date of birth
date of diagnosis
date of written informed consent
eligibility criteria


4. Participating parties



Principal Investigator(s)

Ms. Dr. B. Eichhorst (Klinikum der Universität zu Köln)


Co-Investigator(s)

Prof. Dr. M.H.J. van Oers (AMC)


Coordinating Investigator(s)

Mw. dr. A.M.H. Janssens (UZ Gasthuisberg)
Dhr. Dr. A.P. Kater (AMC)


Monitor - Study Specific

Mw. T. van de Klundert (Erasmus MC - Daniel)
MonitorTeamCTC (Erasmus MC - Daniel)


Principal investigator

Dr. B. Eichhorst


Coordinating investigator(s)

Dr. A. Kater (a.p.kater@amc.uva.nl)
Dr. R. van Oers (m.h.vanoers@amc.uva.nl)


Trial manager

P. Cornelisse (p.cornelisse@erasmusmc.nl)


Central data management

GCLLSG (CRF package will be send out per patient, based on randomized arm but is also available in PDF).


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Stuivenberg
0
BE-Brugge-Algemeen Ziekenhuis St. Jan
0
BE-Ieper-Jan Yperman Ziekenhuis
0
BE-Leuven-UZ Gasthuisberg
0
BE-Roeselare-AZDelta
0
NL-Amersfoort-Meander MC
0
NL-Amsterdam-AMC
0
NL-Amsterdam-VUMC
0
NL-Arnhem-Ziekenhuis Rijnstate
0
NL-Breda-Amphia ziekenhuis, locatie Langendijk
0
Show 20 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


 Protocol

 Patient Information & IC form (NL)



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