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Clinical picture: CLL (Chronical Lymfatic Leukemia)
Trial: HOVON 140 CLL
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms
02MAY2017_First site (AMC) has been activated! Please note that you can find all participating sites and whether or not they are activated in the section Registration & randomization of patients.
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 (firstname.lastname@example.org)
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.
GCLLSG sponsor. HOVON, SAKK, Nordic CLL group
Type of study
Prospective randomized Phase III study
Type of monitoring for this study
Target number of patients
Date of first EC&CA submission
Date of activation
NL EC: 06FEB2017
BE EC: 31MAR2017
NL CA: 19DEC2016
BE CA: 26JAN2017
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
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.
- Patients with an estimated creatinine clearance just under 70ml/min may be eligible if a measured creatinine clearance (based on 24 hour urine collection or other reliable method) is > 70 ml/min. 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.
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
Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/
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
History of stroke or intracranial hemorrhage within 6 months prior to
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
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.
Prisoners or subjects who are institutionalized by regulatory or court
Persons who are in dependence to the sponsor or an investigator.
3. Registration (& randomization) of patients
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 Ulrich Jäger Count Wien 3
BE Ka Lung Wu Count Antwerpen 1
DE Walter Verbeek Count Bonn 1
DE Clemens Schulte Count Dortmund 2
DE Johannes Schetelig Count Dresden 1
DE Thomas Illmer Count Dresden 5
DE Peter Staib Count Eschweiler 2
DE Rainer Claus Count Freiburg 2
DE Mark-Oliver Zahn Count Goslar 1
DE Ulrike Soeling Count Kassel 4
DE Matthias Ritgen Count Kiel 1
DE Christoph van Roye Count Koblenz 2
DE Barbara Eichhorst Count Köln 4
DE Lothar Müller Count Leer 1
DE Kathleen Jentsch-Ulrich Count Magdeburg 1
DE Manfred Hensel Count Mannheim 1
DE Maria Theresia Keller Count Mayen 1
DE Ulrich Graeven Count Mönchengladbach 3
DE Christian Bogner Count München 1
DE Clemens Wendtner Count München 1
DE Holger Hebart Count Mutlangen 3
DE Tobias Gaska Count Paderborn 4
DE Alexander Kroeber Count Regensburg 1
DE Sebastian Böttcher Count Rostock 1
DE Matthias Vöhringer Count Stuttgart 2
DE Stephan Stilgenbauer Count Ulm 3
DE Björn Schöttker Count Würzburg 5
DK Lisbeth Enggaard Count Herlev 1
DK Carsten Utoft Niemann Count Kopenhagen 9
DK Henrik Frederiksen Count Odense 2
NL A.P. Kater Count Amsterdam 2
NL M. Hoogendoorn Count Leuwarden 1
NL D.E. Issa Count s-Hertogenbosch 1
SE Gunnar Juliusson Count Lund 2
Dutch and Belgium site numbers:
BE - Antwerpen - ZNA ___nr: 2394 ACTIVATED
BE - Brugge - St. Jan zkh ___nr: 721
BE - Brussel - St. Luc ___nr: 743
BE - Leuven - UZ Gasthuisberg ___nr: 736 ACTIVATED
BE - Roeselare - AZ Delta ___nr: 2396
BE - Yper - Jan Yperman zkh ___nr: 2407
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
NL - Cappelle ad Ijsel - IJsselland zkh ___nr: 1771
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
NL - Eindhoven - MMC ___nr: 1933
NL - Enschede - MST ___nr: 1356
NL - Gouda - Groene Hart zkh ___nr: 2383
NL - Groningen - UMCG ___nr: 1777
NL - Hoofddorp - Spaarne Gasthuis ___nr: 2398
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
NL - Nijmegen - Radboud UMC ___nr: 2385 ACTIVATED
NL - Rotterdam - Maasstad zkh ___nr: 1808
NL - Sneek - Antonius zkh ___nr: 2401
NL - Terneuzen - ZorgSaam zkh ___nr: 1807
NL - Tilburg - ETZ ___nr: 2402
NL - Utrecht - UMCU ___nr: 2386
NL - Venlo - VieCuri MC ___nr: 2387
NL - Zaandam - Zaans MC ___nr: 2388
NL - Zwolle - Isala ___nr: 1358 ACTIVATED
Registration criteriaThe following information will be requested:
name caller/responsible investigator
date of birth
date of diagnosis
date of written informed consent
4. Participating parties
Dr. B. Eichhorst
Dr. A. Kater (email@example.com)
Dr. R. van Oers (firstname.lastname@example.org)
P. Cornelisse (email@example.com)
Central data management
GCLLSG (CRF package will be send out per patient, based on randomized arm).