NAUT (CAMN107ADE22T) = Efficacy of nilotinib in inducing persistence of molecular remission after second or third TKI stop [Europe]
Study title
Efficacy of nilotinib in inducing persistence of molecular remission after second or third TKI stop
Scientific title
Multicenter prospective trial after first or second 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 or third time (ClinicalTrials.gov NCT02917720; 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 first or second 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 attempt stopping 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
MCC-Studienzentrale, III. Med. Klinik
Medizinische Fakultät Mannheim der Universität Heidelberg
68167 Mannheim
Principal investigator
Prof. Dr. Susanne Saußele
MCC-Studienzentrale, III. Med. Klinik
Medizinische Fakultät Mannheim der Universität Heidelberg
68167 Mannheim
Additional information
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
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. Cornelius Waller
Hugstetter Str. 55
79108 Freiburg
Goslar
MVZ Onkologische Kooperation Harz
Dr. Mark-Oliver Zahn
Kösliner Straße 14
38642 Goslar
Greifswald
Universitätsmedizin Greifswald
Klinik Innere Medizin C / Hämatologie und Onkologie
Prof. Dr. Christian Andreas Schmidt
Ferdinand-Sauerbruchstraße
17475 Greifswald
Halle (Saale)
Universitätsklinikum Halle
Universitätsklinik und Poliklinik für Innere Medizin IV
PD Dr. med. Haifa Kathrin Al-Ali
Ernst-Grube-Str. 40
06120 Halle (Saale)
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
Kempten
Klinikum Kempten
Hämatologie, Onkologie und Palliativmedizin
PD Dr. med. Christian Langer
Robert-Weixler- Straße 50
87439 Kempten
Köln
Gemeinschaftspraxis für Onkologie und Hämatologie
Prof. S. Schmitz, Dr. Steinmetz, Dr. Severin
Dr. med. Hans Tilman Steinmetz
Sachsenring 69
50677 Köln
Mannheim
MCC-Studienzentrale, III. Med. Klinik
Medizinische Fakultät Mannheim der Universität Heidelberg
Prof. Dr. Susanne Saußele
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
Dr. med. Peter Herhaus
Ismaninger Str. 22
81675 München
Mutlangen
Klinikum Ostalb, Stauferklinikum Schwäbisch Gmünd
Zentrum für Innere Medizin
Prof. Dr. Holger Hebart
Wetzgauer Str. 85
73557 Mutlangen
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
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
Not yet 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 (ClinicalTrials.gov NCT03573596; 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 description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
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
Lino Teichmann
Essen
Joachim Göthert
Mannheim
Susanne Saußele (National Coordinator)
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)
Tromsø
Tromsø University Hospital
Anders Vik
Trondheim
St Olavs Hospital-Trondheim University Hospital
Henrik Hjorth Hansen
Sweden
Linköping
Linköping University Hospital
Kourosh Lofti and Arta Dreimane
Luleå
Sunderby Sjukhus
Anneli Enblom-Larsson
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, ClinicalTrials.gov NCT04043676)
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
Multiple
Additional information
Study description in the EU Clinical Trials Register which is hosted by the European Medicines Agency (EMA)
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
Study centers / principal investigators
Spain
Badalona, Barcelona, 08916
Hospital Trials i Pujol
Dr. Blanca Xicoy
Barcelona, 08035
Hospital Vall D'Hebron
Dr. Guillermo Orti
Las Palmas De Gran Canaria, 35010
Hospital Universitario de Gran Canarias Dr. Negrin
Dr. Maria Teresa Gomez
Madrid, 28006
Hospital Unversitario de la Princesa
Juan Luis Steegmann, MD PhD
Madrid, 28034
Hospital Universitario Ramon y Cajal
Valentin Garcia Gutierrez, MD PhD
Madrid, 28041
Hospital Universitario Doce de Octubre
Rosa Ayala, MD PhD
Málaga, 29010
Hospital Regional de Malaga
Dr. Antonio Jimenez
Salamanca, 37007
Hospital Universitario de Salamanca
Fermin Sanchez-Guija, MD PhD
Valencia, 46010
Hospital Clinico Universitario de Valencia
Dr. Juan Carlos Hernandez Boluda
ENDURE = Efficacy and Safety of AOP2014 With CML Patients in Remission [France, Germany]
Study title
ENDURE - Efficacy and Safety of AOP2014 With CML Patients in Remission (ENDURE-CML-IX)
Scientific title
Efficacy and safety of pegylated-proline-interferon alpha 2B (AOP2014) in maintaining deep molecular remission in patients with chronic myeloid leukemia (CML) who discontinue ABL-kinase inhibitory therapy - a randomized phase II, multicenter trial with post-study follow-up (EudraCT no. 2016-001030-94,ClinicalTrials.gov NCT03117816)
Indication and most important inclusion criteria
This study includes male or female patients who:
- are at least 18 years old
- have been diagnosed with BCR-ABL-positive, chronic myeloid leukemia in chronic phase
- have been treated with a tyrosine kinase inhibitor (TKI) for at least 3 years
- have had confirmation of deep molecular remission of MR4 or better (MR4.5, MR5) at least three times within the last year before study entry.
Patients who failed to discontinueTKI in a prior discontinuation attempt are eligible for this study. Additional criteria may apply.
Short description of intervention
Previous clinical studies have shown that about half of all CML patients who achieved good response on long-term therapy manage to stop TKI treatment permanently. Unfortunately, it is not possible to predict whether discontinuation will be successful or not.
The objective of this study is to find out whether temporary treatment with ropeginterferon (AOP2014) can activate the immune system to prevent loss of major molecular remission in CML patients, who discontinue TKI treatment in deep molecular remission of MR4 or better (MR4.5, or MR5).
In this study, patients will be randomly assigned to one of two treatment groups:
Patients in Group A will receive ropeginterferon in the first month after enrolment together with the TKI. After this first month, the TKI therapy will be stopped and paitens will receive ropeginterferon for the next14 months. Ropeginterferon is injected with a pre-filled auto-injection pen under the skin every 2 weeks. It is very well tolerated.
Similar as in the Group A, patients in Group B will discontinue TKI therapy one month after randomization. From then on patients will receive no further CML treatment.
Patients will be closely monitored and treatment outcomes will be assessed.
Type of study
Treatment discontinuation trial
Current status
Recruiting
Study sponsor
Philipps University Marburg Medical Center
in collaboration with
Deutsche Krebshilfe e.V., Bonn (Germany)
AOP Orphan Pharmaceuticals AG
Scientific lead / contact
Prof. Dr. med. Andreas Burchert, Marburg
Principal investigator
Multiple
Additional information
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
Study centers / principal investigators
France
Bordeaux
Institut Bergonié
Gabriel Etienne, MD
Bordeaux, 33076
Lyon
Centre Léon Bérard
Franck-Emmanuel Nicolini, MD
Lyon, 69008
Vandœuvre-lès-Nancy
CHRU Nancy/Brabois
Agnès Guerci-Bresler, MD
Vandœuvre-lès-Nancy, 54500
Germany
Aachen
Universitätsklinikum RWTH Aachen
Martina Crysant, MD
527074 Aachen
Aschaffenburg
Martine Klausmann, MD
63739 Aschaffenburg
Berlin
Universitätsmedizin Berlin Charite- Campus Virchow Klinikum
Prof. Philipp Le Coutre
13353 Berlin
Bonn
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III
Dr. Jai-Jün Shiue
53105 Bonn
Bremen
Klinikum Bremen Mitte, Medizinische Klinik I
Dr. Mathhias Bormann
28177 Bremen
Dresden
BAG / Onkologische Gemeinschaftspraxis
PD Dr. Thomas Illmer
01307 Dresden
Düsseldorf
Universitätsklinikum Düsseldorf
Prof. Norbert Gattermann
40225 Düsseldorf
Erlangen
Universitätsklinikum Erlangen
Prof. Stefan Krause
91054 Erlangen
Essen
Universitätsklinikum Essen, Klinik für Hämatologie
Dr. Joachim Goethert
45147 Essen
Frankfurt
Klinikum der Goethe Universität, Medizinische Klinik II
Dr. Fabian Lang
60590 Frankfurt
Hamburg
Universitätsklinikum Hamburg Eppendorf
Dr. Philippe Schafhausen
20246 Hamburg
Hamm
Evangelisches Krankenhaus Hamm gGmbH
Dr. Elisabeth Lange
59063 Hamm
Jena
Universitätsklinikum Jena
Prof. Andreas Hochhaus
07747 Jena
Koblenz
Institut für Versorgungsforschung in der Onkologie GbR
Dr. Christoph Lutz
56068 Koblenz
Leipzig
Universitätsklinikum Leipzig
Dr. Georg-Nikolaus Franke
04103 Leipzig
Mainz
Johannes-Gutenberg-Universität
III. Medizinische Klinik
PD Dr. Thomas Kindler
55131 Mainz
Mannheim
Universitätsmedizin Mannheim
Prof. Susanne Saußele
68169 Mannheim
Marburg
Universitätsklinikum Gießen und Marburg GmbH
Prof. Andreas Burchert
35043 Marburg
München
III. Medizinische Klinik TUM
Klinikum rechts der Isar
PD Dr. Philipp Jost
81675 München
Münster
Universitätsklinikum Münster
Dr. Eva Schmidt
48149 Münster
Tübingen
Med. Univ.-Klinik II
Prof. Robert Möhle
72076 Tübingen
Ulm
Universitätsklinikum Ulm
PD Dr. Frank Stegelmann
89081 Ulm
Würzburg
Zentrum für Innere Medizin
Dr. Maria-Elisabeth Goebler
97080 Würzburg
ResToP = Reinduction and Second Stop of TKI With Ponatinib in CML [Spain]
Study title
ResToP = Study to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response
Scientific titleStudy to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response
Multicenter, Open-Label, Single Arm, Phase II Exploratory Study to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response (ResToP) (ClinicalTrials.gov no. NCT04160546, EudraCT no. 2018-003281-14)
Indication and most important inclusion criteria
This study includes patients who:
- are at least 18 years old
- have an Eastern Co-Operative Group (ECOG) status of 0, 1 or 2
- have been diagnosed with BCR-ABL positive and Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase (CP-CML)
- lost deep molecular response (MR4) after a first attempt of stopping tyrosine kinase inhibitor (TKI) treatment, restarted TKI again and then regained and maintained confirmed MR4 for more than one year
- have adequate end organ function
Other criteria may apply.
Short description of intervention
In this study, patients will be treated with ponatinib 15 mg/day plus acetyl salicylic acid (ASA) 100 mg/day for 104 weeks. After that, ponatinib and ASA will be stopped.
The study will determine the rate of successful treatment-free remission (TFR) within the first 52 weeks after stopping ponatinib treatment in patients who achieved MR4.
Type of study
7. Treatment discontinuation trials
Current status
Recruiting
Study sponsor
Fundacion CRIS de Investigación para Vencer el Cáncer
in collaboration with:
Incyte Biosciences UK
Apices Soluciones S.L.
Scientific lead / contact
Ana Moreno
Apices Soluciones S.L.
Principal investigator
Joaquín Martínez López, MD
Hospital Universitario 12 de Octubre
Valentín García Gutierrez, MD
Hospital Universitario Ramon y Cajal
Juan Carlos Hernández Boluda, MD
Hospital Clínico de Valencia
Additional information
Study description in the EU Clinical Trials Register which is hosted by the European Medicines Agency (EMA)
Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health
Study centers / principal investigators
Spain
Badalona
Institut Català d´oncologia Badalona (ICO)
Las Palmas
Hospital Universitario de Gran Canaria Dr. Negrín
Madrid
Hospital Ramón y Cajal
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario La Paz
ontact: Raquel De Paz
Murcia
Hospital General Universitario J.M. Morales Meseguer
Málaga
Complejo Hospitalario Regional de Málaga
Málaga
Hospital Virgen de La Victoria
Salamanca
Hospital Universitario de Salamanca
Valencia
Hospital Clínico Universitario de Valencia