NAUT (CAMN107ADE22T) = Efficacy of nilotinib in inducing persistence of molecular remission after second TKI stop [Europe]
Study title
Efficacy of nilotinib in inducing persistence of molecular remission after second TKI stop
Scientific title
Multicenter prospective trial after first unsuccessful treatment discontinuation in chronic myeloid leukemia estimating the efficacy of nilotinib in inducing the persistence of molecular remission after stopping tyrosine kinase inhibitors a second time (EudraCT no. 2015-004998-33)
Indication and most important inclusion criteria
This study includes patients from 18 years of age with chronic myeloid leukemia (CML) who have had a molecular relapse after a prior attempt to stop therapy with a tyrosine kinase inhibitor (TKI) therapy and who have been treated for at least one year with any TKI after the first stop.
Short description of intervention
Patients will be treated with nilotinib 600 mg/day for at least two years. Patients who achieve deep molecular remission (MR4.5 or better) at the end of treatment can make a second attempt to stop TKI treatment.
The main objective of the study is to assess whether more patients maintain at least major molecular remission at 12 and 36 months after stopping TKI therapy.
Type of study
Treatment discontinuation trial
Current status
recruiting
Study sponsor
University of Heidelberg, Germany, with financial support from Novartis GmbH
Scientific lead / contact
Prof. Dr. Susanne Saußele
III. Med. Klinik
Medizinische Fakultät Mannheim der Universität Heidelberg
68169 Mannheim, Germany
Principal investigator
Prof. Dr. Susanne Saußele
III. Med. Klinik
Medizinische Fakultät Mannheim der Universität Heidelberg
68169 Mannheim, Germany
Additional information
Study centers / principal investigators
Germany
Aachen
Universitätsklinikum der RWTH Aachen
Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
Prof. Dr. med. Tim Henrik Brümmendorf
Pauwelsstr. 30
52074 Aachen
Ansbach
Ambulantes Onkologie Zentrum
Dr. med. Markus Hahn
Schöneckerstr. 4
91522 Ansbach
Aschaffenburg
Studienzentrum Aschaffenburg
Dr. med. Martine Klausmann
Elisenstr. 26
63739 Aschaffenburg
Bayreuth
Klinikum Bayreuth GmbH
Medizinische Klinik IV
PD Dr. med. Alexander Kiani
Preuschwitzer Str. 101
95445 Bayreuth
Berlin
Charité – Universitätsmedizin Berlin, CVK
Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie
Professor Dr. med. Philipp le Coutre
Augustenburger Platz 1 (Mittelallee 11)
13353 Berlin
Chemnitz
Klinikum Chemnitz gGmbH
Klinik für innere Medizin III
Dr. med. Mathias Hänel
Flemmingstr. 2
09113 Chemnitz
Dresden
Onkozentrum Dresden
Dr. Göhler/Dörfler/Boldt
DM Steffen Dörfel
Leipziger Str. 118
01127 Dresden
Essen
Universitätsklinikum Essen
Klinik für Hämatologie
Dr. med. Joachim R. Göthert
Hufelandstr. 55
45147 Essen
Esslingen
Onkologische Schwerpunktpraxis
Dr. med. Robert Eckert
Berliner Str. 4
73728 Esslingen
Frankfurt
Centrum für Hämatologie und Onkologie Bethanien
Prof. Dr. med. Hans Tesch
Im Prüfling 17-19
60389 Frankfurt
Freiburg
Universitätsklinikum Freiburg
Innere Medizin I
Prof. Dr. med. Nikolas von Bubnoff
Hugstetter Str. 55
79108 Freiburg
Greifswald
Universitätsmedizin Greifswald
Klinik Innere Medizin C / Hämatologie und Onkologie
Prof. Dr. Christian Andreas Schmidt
Ferdinand-Sauerbruchstraße
17475 Greifswald
Hannover
Medizinische Hochschule Hannover
Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
PD Dr. med. Christian Könecke
Carl-Neuberg-Str. 1
30625 Hannover
Heilbronn
Schwerpunktpraxis Onkologie
Dr. med. Jolanta Dengler
Allee 40
74072 Heilbronn
Jena
Universitätsklinikum Jena, Klinik und Poliklinik für Innere Medizin II
Hämatologie/Onkologie/ Stammzelltransplantation
Prof. Dr. med. Andreas Hochhaus
Erlanger Allee 101
07740 Jena
Mannheim
Universitätsmedizin Mannheim
III. Med. Klinik Mannheim
Prof. Dr. med. Susanne Saußele
Theodor-Kutzer-Ufer 1-3
68167 Mannheim
Marburg
Universitätsklinikum Gießen und Marburg,
Standort Marburg
Klinik für Hämatologie, Onkologie und Immunologi
Prof. Dr. med. Andreas Burchert
35043 Marburg
München
Klinikum rechts der Isar
Klinik und Poliklinik für innere Medizin III
PD Dr. med. Philipp Jost
Ismaninger Str. 22
81675 Munich
Rostock
Universitätsmedizin Rostock
ZIM III - Hämatologie, Onkologie, Palliativmedizin
Prof. Dr. med. Christian Junghanß
Ernst-Heydemann-Straße 6
18057 Rostock
Villingen Schwenningen
Schwarzwald-Baar Klinikum
Klinik für Innere Medizin II
Prof. Dr. med. Paul Graf La Rosée
Klinikstraße 11
78052 Villingen-Schwenningen
The Netherlands
VU University Medical Center Amsterdam
Dr. Jeroen Janssen
1081 HV Amsterdam
ENESTPath Patient's Voice Italian Substudy [Italy]
ENESTPath Patient's Voice Italian Substudy [Italy]
ENESTPath Patient's Voice Italian Substudy
Scientific title
CML patient's voice: A pilot sub-study exploring the emotional experience of patients during CAMN107AIC05 Study - Italian substudy of ENESTPath (clinicaltrials.gov NCT01743989, EudraCT 2012-005124-15)
Indication and most important inclusion criteria
Patients in consolidation study phase of ENESTPath who will perform visit 6 at the time of sub-study activation
Short description of intervention
Patients from Italian centres participating in ENESTPath will undergo specific Quality of Life and psychological assessments during the consolidation and treatment-free remission phase.
The following tools will be used:
- Patient Diary
- EORTC QLQW-C30: a questionnaire to assess the quality of life of cancer patients
- EORTC-CML: a questionnaire to assess the quality of life of CML patients
- Sixteen Personality Factor Questionnaire (16PF): a self-report personality test;
- Symptom Checklist 90 (SCL.90-R): a self reported questionnaire
Type of study
5. Treatment discontinuation trials
In a single country
Current status
Starting to obtain Ethics Committee approvals
Study sponsor
Novartis
Scientific lead / contact
Claudia Galimberti Novartis Farma S.p.A.
Principal investigator
Luca Dezzani Novartis Farma S.p.A.
Additional information
...
Study centers / principal investigators
Italian centers participating in ENESTPath
PIO2STOP = Second STOP After Pioglitazone Priming in CML Patients [France]
Study title
Second STOP After Pioglitazone Priming in CML Patients(PIO2STOP) [France]
Scientific title
Combination study of pioglitazone and tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients after failure of a first TKI discontinuation attempt to in order to prepare a new stop (clinicaltrials.gov NCT02889003)
Indication and most important inclusion criteria
This study includes patients who:
- have chronic myeloid leukemia (CML) in any phase
- are at least 18 years old
- have been treated with imatinib, dasatinib, nilotinib or bosutinib before
- have discontinued tyrosine kinase inhibitor (TKI) treatment during a first stop trial and thereafter lost MMR
- have achieved deep molecular response (MR4.5)
- have adequate liver and kidney function
Short description of intervention
The purpose of this study is to evaluate whether the combination of pioglitazone with a tyrosine kinase inhibitor (TKI) is safe in patients who have lost major molecular response (MMR) after stopping a first TKI.
Study participants will be started on or continue with the same TKI and at the same dose as before discontinuation. They will also receive pioglitazone 30 mg once daily. After 2 months the pioglitazone dose will be increased to 45 mg once daily in patients who do not have any adverse events of grade 2 or worse.
Patients need to have achieved deep molecular response (MR4.5) before inclusion. They will receive pioglitazone and the TKI for 6 months in the study and will then have the option of stopping the combination treatment altogether. They will then be monitored for 2 years to see if they remain well without any treatment. Patients will be followed up for 5 years.
Type of study
Treatment discontinuation trial
Current status
Recruiting
Study sponsor
Hôpitaux de Versailles, Hôpital Mignot, France
Scientific lead / contact
Pr Philippe Rousselot
Centre Hospitalier de Versailles
France
Principal investigator
Pr Philippe Rousselot
Centre Hospitalier de Versailles
France
Additional information
...
Study centers / principal investigators
France
Le Chesnay, 78157
Centre Hospitalier de Versailles
Hôpital André Mignot
Service de Médecine B Hématologie-Oncologie
Pr Philippe Rousselot
DASTOP-2 (CA180-655) = Second treatment stop [Denmark, Finland, France, Germany, Sweden, Norway, The Netherlands]
Study title
DASTOP-2 = A multicenter trial where patients with CML stop medication a second time
Scientific title
Persistence of major molecular remission in chronic myeloid leukemia after a second stop of TKI treatment in patients who failed an initial stop attempt: A prospective multicenter study (EudraCT 2016-004106-34)
Indication and most important inclusion criteria
This study includes male or female patients who:
- are at least 18 years old
- have chronic myeloid leukemia (CML) in chronic phase (CP) with confirmed presence of the BCR/ABL1 gene
- who have had a molecular relapse after attempting to stop therapy with a tyrosine kinase inhibitor (TKI) within the EUROSKI study or outside the study but according to EUROSKI procedures. Patients who attempted stopping outside the study must have received a TKI for at least 3 years before the first stop, including dasatinib in this study during the last 2 years. Patients must have been in deep molecular response (MR4) for at least 1 year before stopping.
- who have been treated with any TKI for at least 1 year after having failed a first attempt to stop treatment with a TKI
Short description of intervention
The purpose of this study is to assess treatment-free remission (persistence of major molecular remission) after a second attempt to stop TKI treatment
Type of study
7. Treatment discontinuation trials
Current status
Recruiting
Study sponsor
Uppsala University Hospital, Sweden,
with financial support from BMS
Scientific lead / contact
Ulla Olsson-Strömberg, Uppsala University Hospital
Principal investigator
Ulla Olsson-Strömberg, Uppsala University Hospital
Additional information
Study description in the EU Clinical Trials Register which is hosted by the European Medicines Agency (EMA)
Study centers / principal investigators
Denmark
Aarhus
Aarhus University Hospital
Jesper Stentoft
Odense
Odense University Hospital
Andreja Dimitrijevic (National Coordinator)
Finland
Helsinki
Department of Hematology Helsinki University Hospital
Satu Mustjoki (National Coordinator) and Perttu Koskenvesa
France
Créteil
Centre Hospitale-Universitaire, Créteil
Lydia Roy (National Coordinator)
More centers are going to join in France later.
Germany
Bonn
Dominik Wolf (National Coordinator)
Essen
Joachim Göthert
Mannheim
Susanne Saußele
Marburg
Anderas Burchert
Villingen-Schwenningen
Paul Graf la Rosée
Norway
Bergen
Haukeland University Hospital
Bjørn Tore Gjertsen
Oslo
Oslo University Hospital
Tobias Gedde Dahl
Stavanger
Stavanger University Hospital
Waleed Majeed (National Coordinator)
Trondheim
St Olavs Hospital-Trondheim University Hospital
Henrik Hjorth Hansen
Sweden
Linköping
Linköping University Hospital
Kourosh Lofti and Arta Dreimane
Lund
Lund University Hospital
Johan Richter, Anna Lubking and Elena Holm
Örebro
Örebro University Hospital
Erik Ahlstrand
Stockholm
Karolinska Hospital
Leif Stenke and Lotta Ohm
Umeå
Umeå University Hospital
Berit Markevärn
Uppsala
Uppsala University Hospital (Akademiska)
Stina Söderlund, Ulla Olsson Strömberg (Principal Investigator)
The Netherlands
Amsterdam
Jeroen Janssen (National Coordinator)
Dordrecht
Peter Westerweel
Nijmegen
Nicole Blijlevens
Rotterdam
Peter Boekhorst
PonaZero = Effect of Consolidation Treatment with Ponatinib on TFR Rate [Spain]
Study title
PonaZero = Effect of Consolidation Treatment with Ponatinib on Treatment-free Remission Rate in Patients With Chronic Phase Chronic Myeloid Leukemia (CML) with Deep Molecular Response
Scientific title
Multicenter, open-label, randomized phase III pilot study to evaluate the effect of a one-year consolidation treatment with ponatinib at two-dose ranges on free-remission rate in patients with Philadelphia-positive chronic myeloid leukemia, who had previously achieved a deep molecular response (EudraCT no. 2017-004565-27)
Indication and most important inclusion criteria
This study includes patients who:
- have BCR-ABL positive chronic myeloid leukemia in chronic phase (CP-CML)
- have been on imatinib treatment for a minimum of 4 years with confirmed stable deep molecular response (MR4) for a minimum of 12 months prior to enrolment
- are at least 18 years old
- have not had a prior accelerated phase/blast crisis (AP/BC) or stem cell transplant (SCT)
- have an Eastern Co-Operative Group (ECOG) status of 0-2
Short description of intervention
This is a pilot study to determine the rate of successful treatment-free remission (TFR) in patients who achieved and maintained molecular response 4 (MR4) on ponatinib following at least 4 years of imatinib therapy. Patients who maintain MR4 during the 52-week ponatinib onsolidation phase can attempt stopping ponatinib and will continue in the 104-week TFR phase.
Type of study
7. Treatment discontinuation trials
Current status
Recruiting
Study sponsor
FUNDACIÓN TEÓFILO HERNANDO, Edificio Claid
Parque Científico de Madrid
Calle Faraday, 7, Campus de Cantoblanco, 28049 Madrid
Scientific lead / contact
Gutierrez, Garcia
Principal investigator
Additional information
Study description in the EU Clinical Trials Register which is hosted by the European Medicines Agency (EMA)
Study centers / principal investigators
Spain
up to 11 sites
QMH-CML-001 = Cessation of TKI in CML [Hong Kong]
Study title
QMH-CML-001 = Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic Phase Chronic Myelogenous Leukaemia
Scientific title
Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia Who Achieve Stable Deep Molecular Response (ClinicalTrials.gov NCT03131986)
Indication and most important inclusion criteria
This study includes male or female patients who:
- are at least 18 years old
- have been diagnosed with chronic myeloid leukemia in chronic phase
- have been treated with a tyrosine kinase inhibitor (TKI) in first line, or in second line due to intolerance of another first-line TKI
- have been on treatment with the same TKI for at least 3 years and had deep molecular response (MR4.5) for at least 2 years
Short description of intervention
International clinical trials have demonstrated that about 40-60% of CML patients who achieved deep molecular response on TKI manage to remain in sustained treatment-free remission after stopping treatment. Experience of discontinuing TKI treatment is lacking in Hong Kong.
The objective of this single-arm study is to collect local experience with TKI discontinuation in patients with CML in chronic phase who are treated with TKIs and remain in stable deep molecular response for at least two years. Patients who stop TKI treatment will be closely monitored and treatment outcomes will be reassessed.
Type of study
Treatment discontinuation trial
Current status
Recruiting
Study sponsor
The University of Hong Kong
Scientific lead / contact
Professor Yok-lam Kwong
The University of Hong Kong
Principal investigator
Contact: Yuk Man Cheung, MBBS(HK)
Additional information
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
Study centers / principal investigators
Hong Kong
Yuk Man Cheung, MBBS(HK)
Queen Mary Hospital, Hong Kong