ACTIW = Therapies in Combination or Sequentially with TKIs in CML-CP Patients in Complete Cytogenic Remission [France]

Study title

Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors (TKIs) in Chronic Phase Chronic Myelogenous Leukemia Patients in Complete Cytogenic Remission (CCR) (ACTIW) [France]

Scientific title

Candidate Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors in Chronic Phase Chronic Myelogenous Leukemia Patients in CCR Without Achieving a Deep Molecular Response: an Adaptative Trial Based on a Drop Loser Design (ClinicalTrials.gov NCT02767063)

Indication and most important inclusion criteria

This study includes patients who:
- are at least 18 years old
- have Philadelphia chromosome positive (Ph+) and BCR-ABL1+ chronic myeloid leukemia in chronic phase (CP-CML)
- have been treated imatinib, nilotinib, dasatinib, bosutinib or ponatinib for more than 2 years overall
- have not switched between tyrosine kinase inhibitors within the last 3 months
- have achieved complete cytogenetic response (CCR) (BCR-ABL less than or equal 1% on the International Scale)
- have an Eastern Co-Operative Group (ECOG) status of 0-2
- have adequate liver and kidney function

Short description of intervention

The purpose of this study is to evaluate whether combination of a tyrosine kinase inhibitor (TKI) with another study drug can help achieve deep response (MR4.5).

Patients will receive either a TKI alone (imatinib, nilotinib, dasatinib, bosutinib or ponatinib at the same daily dose and schedule as during the last 3 months before inclusion in the study) or a TKI (imatinib, nilotinib, dasatinib, bosutinib or ponatinib at the same daily dose and schedule as during the last 3 months before inclusion in the study) in combination with another drug.

The first arm (TKI alone versus TKI + combination with pioglitazone) has been completed.

Additional treatment groups with other combinations are planned and include:
- a TKI in combination with avelumab
- a TKI in combination with pegylated interferon
- a TKI in combination with arsenic trioxide
- a TKI in combination with Homoharringtonine-
- a TKI in combination with anti-PD-L1 antibody

Type of study

Therapy optimization 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 description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health

Study centers / principal investigators

France

Angers, 49033
Service de Médecine D
CHU d'Angers
Prinicpal Investigator: Martine Gardembas

Annecy
Prinicpal Investigator: Pascale Cony-Makhou

Bobigny, 93000
Service Hématologie
Hôp Avicenne
Prinicpal Investigator: Thorsten Braun

Bordeaux, 33076
Institut Bergonié
Prinicpal Investigator: Gabriel Etienne

Caen
CHU Côte de Nacre
Prinicpal Investigator: Hyacynthe Johnson-Ansah

Clermont-Ferrand
CHU Estaing
Prinicpal Investigator: Marc Berger

Créteil, 94010
Service Hématologie Clinique et Thérapie Cellulaire
CHU Henri Mondor
Prinicpal Investigator: Lydia Roy

Le Chesnay, 78157
Centre Hospitalier de Versailles
Hôpital André Mignot
Service de Médecine B Hématologie-Oncologie
Prinicpal Investigator: Pr Philippe Rousselot (Coordinating Investigator)

Lille, 59037
Service des Maladies du Sang
Hôpital Claude Huriez
Prinicpal Investigator: Valérie Coiteux

Limoges
CHU de Limoges
Prinicpal Investigator: Amélie Penot

Lyon, 69374
Service d'Hématologie
Hôpital Edouard Herriot
Prinicpal Investigator: Franck Nicolini

Marseilles, 13273
Service Hématologie
Institut Paoli Calmette
Prinicpal Investigator: Aude Charbonnier

Nantes, 44035
Service d'Hémato-Cancérologie
CHU Hôtel-Dieu
Prinicpal Investigator: Viviane Dubruille

Nice
Hopital l'Archet
Principal Investigator: Eric Jourdan

Nimes, 30029
Service de Hématologie Oncologie
CHU Caremeau
Principal Investigator: Eric Jourdan

Orleans, 45100
Service d'Onco-Hématologie
Hôpital La Source
Principal Investigator: Omar Benbrahim

Paris,75010
Centre D'investigations INSERM CIC9504
Hôpital St Louis
Principal Investigator: Delphine Rea

Paris, 75571
Service de Hématologie Oncologie
CHU St Antoine
Principal Investigator: Simona Lapusan

Poitiers, 86021
Département d'Hématologie et Oncologie et Inserm CIC 1402
CHU de Poitiers
Principal Investigator: Emilie Cayssials

Rennes, 35033
Service Hématologie
CHU de Rennes
Principal Investigator: Martine Escoffre-Barbe

Saint-Cloud
Hôpital René Huguenin
Principal Investigator: Sylvie Glaisner

Toulouse
Institut Universitaire contre le Cancer
Principal Investigator: Françoise HUGUET

Tours, 37000
Service Hémato-Oncologie
CHU de Tours
Principal Investigator: Caroline Dartigeas

ASC4MORE (CABL001E2201) = A Phase II Study of ABL001 in Patients With CML-CP without Deep Molecular Response [Asia, Australia, Europe, North America, South America]

Study title

ASC4MORE (CABL001E2201) = A Phase II Study of Asciminib in Combination With Imatinib for Patients with CML-CP without Deep Molecular Response

Scientific title

A phase 2, multi-center, open-label, randomized study of oral asciminib added to imatinib versus continued imatinib versus switch to nilotinib in patients with CML-CP who have been previously treated with imatinib and have not achieved deep molecular response (EudraCT 2018-001594-24, ClinicalTrials.gov NCT03578367)

Indication and most important inclusion criteria

Male or female patients 18 years and older with Philadelphia chromosome-positive CML in chronic phase who previously received first line treatment with imatinib. Patients can be considered for inclusion in the study if they have BCR-ABL results of more than 0.1% and up to 1% on the international scale (IS) at the screening examination and did not reach deep molecular response (MR4 or better) at any time during prior imatinib treatment. To be eligible for inclusion, patients must have acceptable laboratory values at screening, electrolytes within normal limits, and adequate end-organ function.

Short description of intervention

This is a study of the efficacy and safety of asciminib in addition to imatinib compared to continued imatinib or compared to nilotinib in pre-treated CML-CP patients without a deep level of molecular response on imatinib.

Type of study

Therapy optimization trial

Current status

recruiting

Study sponsor

Novartis Pharmaceuticals

Scientific lead / contact

Novartis Pharmaceuticals

Principal investigator

Novartis Pharmaceuticals

Additional information

Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health 

Study centers / principal investigators

Australia

New South Wales
Novartis Investigative Site
Darlinghurst, 2010

South Australia
Novartis Investigative Site
Adelaide, 5000

Victoria
Novartis Investigative Site
Melbourne, 3000

Austria

Novartis Investigative Site
Graz, 8036

Novartis Investigative Site
Vienna, 1140


Canada

Novartis Investigative Site
Montreal, H1T 2M4


Chile

Novartis Investigative Site
Temuco, Araucania, 4810469

Novartis Investigative Site
Vina del Mar, Valparaiso, 2540364


Czech Republic

Novartis Investigative Site
Brno - Bohunice, 639 01


Denmark

Novartis Investigative Site
Herlev, DK 2730


France

Novartis Investigative Site
Bordeaux, 33076


Germany

Novartis Investigative Site
Berlin, 13353

Novartis Investigative Site
Dresden; 01307

Novartis Investigative Site
Mannheim, 68305


Hong Kong

Novartis Investigative Site
Hong Kong

Italy

Novartis Investigative Site
Milano, 20162

Novartis Investigative Site
Roma, 00161

 


Korea, Republic of

Novartis Investigative Site
Seoul, Seocho Gu, 06591

Novartis Investigative Site
Seoul, 03080

Poland

Novartis Investigative Site
Krakow, 31 531

Novartis Investigative Site
Warszawa, 02 776

Novartis Investigative Site
Wroclaw, 50 367

Portugal

Novartis Investigative Site
Lisboa, 1099 023

Novartis Investigative Site
Porto, 4200-072


Russian Federation

Novartis Investigative Site
Moscow, 125167

Novartis Investigative Site
Moscow, 115284

Novartis Investigative Site
Saint Petersburg, 191024

Novartis Investigative Site
Saint Petersburg, 197341

Spain

Novartis Investigative Site
Sevilla, 41009

Novartis Investigative Site
Madrid, 28034

Novartis Investigative Site
Valencia, 46026

Taiwan

Novartis Investigative Site
Changhua, 50006

Novartis Investigative Site
Taipei, 10002

Novartis Investigative Site
Taoyuan, 33305

United Kingdom

Novartis Investigative Site
London, W12 0HS

Novartis Investigative Site
Oxford, OX3 7LJ

Novartis Investigative Site
Wirral, Merseyside, CH63 4JY

USA

Georgia
Georgia Regents University
Augusta, 30912

Illinois
University of Chicago
Chicago, 60637

Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, 21205

S1712 = Testing the Addition of Ruxolitinib to the Usual Treatment (Tyrosine Kinase Inhibitors) for CML [USA]

Study title

Testing the Addition of Ruxolitinib to the Usual Treatment (Tyrosine Kinase Inhibitors) for Chronic Myeloid Leukemia (S1712)

Scientific title

A Randomized Phase II Study of Ruxolitinib (NSC-752295) in Combination With BCR-ABL Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia (CML) (clinicaltrials.gov NCI-2017-02066; NCT03654768)

Indication and most important inclusion criteria

This study includes patients who:
- are at least 18 years old
- have been diagnosed with chronic phase chronic myeloid leukemia (CML-CP) without any history of progression to accelerated or blast phase CML
- have been receiving treatment with dasatinib or nilotinib as first or second line therapy for a minimum of 6 months prior to registration
- have not received more than 2 tyrosine kinase inhibitors (TKIs) for treatment of CML (hydroxyurea prior to initiation of TKI is allowed)
- have been on their current TKI for a minimum of 6 months prior to randomization
- are expected to remain on the same TKI for the next 12 months
- have adequate liver and kidney function

Other criteria may apply. Please consult your doctor for further details.

Short description of intervention

This study assesses how well ruxolitinib phosphate and dasatinib or nilotinib work in treating patients with chronic myeloid leukemia. Ruxolitinib, dasatinib, and nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Type of study

Therapy optimization trial

Current status

Recruiting

Study sponsor

Southwest Oncology Group
National Cancer Institute (NCI)
Portland, Oregon, USA

Scientific lead / contact

Kendra L. Sweet, MD 

Principal investigator

Kendra L. Sweet, MD

Additional information

Study centers / principal investigators

United States

Southwest Oncology Group
National Cancer Institute (NCI)
Kendra L. Sweet, MD
Portland, Oregon 97239

For details on 517 study locations see study information at clinicaltrials.gov

AIM4CML (CABL001AUS04) = Asciminib monotherapy for patients with CML-CP with and without T315I mutation [USA]

Study title

AIM4CML (CABL001AUS04) = Asciminib monotherapy for patients with CML-CP with and without T315I mutation

Scientific title

An Open Label, Multi-center Phase IIIb Study of Asciminib (ABL001) Monotherapy in Previously Treated Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation (ClinicalTrials.gov NCT04666259)

Indication and most important inclusion criteria

This study includes male or female patients 18 years and older with CML in chronic phase (CML-CP) who meet laboratory values specified in the study protocol.

Eligible patients must have had mutation analysis testing done 6 months before study entry. Patients without the T315I mutation will have received 2 tyrosine kinase inhibitors (TKIs) and patients with the T315I mutation will have received 1TKI before study entry.

Eligible patients must also have adequate end-organ function, and an Eastern Co-Operative Oncology Group (ECOG) status of 0, 1 or 2.

Additional criteria may apply.

Short description of intervention

This is a study of the safety and efficacy asciminib in CML-CP patients without T315I mutation who have had at least 2 prior TKIs and CML-CP patients with the T315I mutation who have had at least 1 prior TKI.

The study consists of three periods: screening and baseline for up to 21 days, treatment with asciminib tablets for up to 72 weeks and a safety follow up period for 30 days.

Patients with CML-CP without T315I mutation will be randomly assigned to either group A or B. Patients with the T315I mutation will be enrolled in group C. During the treatment period, group A will receive aciminib 40 mg twice a day, group B will receive 80 mg once a day and group C will receive 200 mg twice a day.

Type of study

Therapy optimization trial

Current status

Not yet recruiting
First patients are likely to be enrolled in March 2021.

Study sponsor

Novartis Pharmaceuticals

Scientific lead / contact

Novartis Pharmaceuticals

Principal investigator

Novartis Pharmaceuticals

Additional information

Study description in the US register ClinicalTrials.gov, a service of the U. S. National Institutes of Health 

Study centers / principal investigators

Around 40 sites are likely to be involved across the US.

PONTrack = With ponatinib on the track for treatment-free remission in CML [Germany]

Study title

PONTrack = With ponatinib on the track for treatment-free remission in chronic myeloid leukemia (CML XII)

Scientific title

With ponatinib on the track for treatment-free remission in chronic myeloid leukemia (EudraCT 2018-004564-59)

Indication and most important inclusion criteria

Female or male patients 18 years and older with  CML in chronic phase (CP) with BCR-ABL on the International Scale (IS) between 0.5-0.01%.

Patients can be considered for inclusion in the study if they have not achieved MR4 (defined as < 0,01% BCR-ABL IS) or not achieved a stable MR4 (defined as no continuous MR4 in the last 12 months before inclusion) after at least 3 years of treatment with nilotinib, dasatinib and / or bosutinib in first or second line.

Other criteria may apply.

Short description of intervention

Achieving and maintaining deep molecular response (DMR) to CML treatment is a precondition for successfully discontinuing TKI treatment and achieving treatment-free remission (TFR).

Many patients achieve major molecular response (MMR = BCR-ABL1 transcripts below 0,1% on the International Scale). However, quite a few do not reach DMR or stable DMR (MR4 or better = BCR-ABL below 0.01% IS) even after several years of treatment with TKIs.

The PONTrack study opens the possibility of TFR to these patients as treatment with ponatinib, a highly effective third generation TKI, may help achieve DMR. In Germany, ponatinib is approved for the treatment of CML, but only for patients who no longer benefit from other TKIs (TKI failure) or who do not tolerate other TKIs (intolerance), or for patients with evidence of a T315I mutation.

Following inclusion in this study, patients will be treated with ponatinib for two years. Depending on the molecular response to treatment, the initial dose of 30 mg will be reduced to (down to 15 mg) or increased (up to no more than 45 mg). Using the lowest possible dosage and close monitoring are expected to be associated with a clearly lower risk of adverse effects than seen in other studies while treatment efficacy is expected to be the same.

Discontinuation of TKI treatment after achieving DMR will not be attempted within the PONTrack study, but only after patients have completed their participation in this study. Provided patient informed consent, TKI discontinuation data will be collected in a planned registry to gain scientific knowledge.

Type of study

Therapy optimization trial

Current status

Recruiting

Study sponsor

Heidelberg University
with support from Incyte Biosciences International Sàrl

Scientific lead / contact

Prof. Dr. med. Susanne Saußele
Universitätsmedizin Mannheim
III. Medizinische Klinik, MCC-Studienzentrale
68167 Mannheim

Principal investigator

Prof. Dr. med. Susanne Saußele
Universitätsmedizin Mannheim
III. Medizinische Klinik, MCC-Studienzentrale
68167 Mannheim

Additional information

Links to documents such as patient information, trial website etc...

Study description in the EU Clinical Trials Register which is hosted by the European Medicines Agency (EMA)

Study information in German on the website of Deutsche CML Allianz

Study centers / principal investigators

Germany

Universitätsklinikum der RWTH Aachen
Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
Dr. M. Crysandt
52074 Aachen

Klinikum Bayreuth
Medizinische Klinik IV
Prof. Dr. Kiani
95445 Bayreuth

Klinikum Chemnitz
Klinik für Innere Medizin III
PD Dr. M. Hänel
09116 Chemnitz

MVZ Onkologische Kooperation Harz
Dr. Mark-Oliver Zahn
38642 Goslar

Universitätsklinikum Halle
Universitätsklinik und Poliklinik für Innere Medizin IV
PD Dr. Haifa Kathrin Al-Ali
06120 Halle

Onkologisches Ambulanzzentrum Hannover
Prof. Dr. M. Koenigsmann
30171 Hannover

Schwerpunktpraxis Onkologie Heilbronn
PD Dr. Dengler
74072 Heilbronn

Universitätsmedizin Mannheim
III. Medizinische Klinik
Prof. S. Saußele
68167 Mannheim

Klinikum Oldenburg AöR
Universitätsklinik für Innere Medizin - Onkologie und Hämatologie
Studienzentrum
Andreas Voß
26133 Oldenburg

Universitätsmedizin Rostock, ZIM II
Klinik für Hämatologie, Onkologie und Palliativmedizin
Prof. C. Junghanß
18057 Rostock

Universitätsklinikum Ulm
Klinik für Innere Medizin III
Priv.-Doz. Dr. med. Frank Stegelmann
Albert-Einstein-Allee 23
89081 Ulm

 

 

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