Front-line Treatment of BCR-ABL+ Chronic Myeloid Leukemia (CML) With Dasatinib (CML1113)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01761890
First received: January 3, 2013
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

The GIMEMA CML Working Party promotes a multicentric, observational, non company sponsored, prospective study of Chronic Myeloid Leukemia (CML) patients treated frontline with dasatinib. Patients will be followed for 5 years. This study will help the definition of guidelines for the treatment of CML patients in early phases.

The primary objective of the study is to describe, in the clinical practice, the rate of events leading to permanent discontinuation after 2 years of treatment with dasatinib as frontline therapy in newly diagnosed CML patients.


Condition Intervention
Chronic Myeloid Leukemia
Behavioral: Dasatinib discontinuation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Front-line Treatment of BCR-ABL+ Chronic Myeloid Leukemia (CML) With Dasatinib. An Observational Multicentric Study.

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Number of dasatinib permanent discontinuing patients. [ Time Frame: After 2 years from study entry. ] [ Designated as safety issue: No ]
    The cumulative rate of dasatinib permanent discontinuation by 2 years.


Secondary Outcome Measures:
  • Number of dasatinib permanent discontinuing patients. [ Time Frame: After 5 years from study entry. ] [ Designated as safety issue: No ]
    The cumulative rate of dasatinib permanent discontinuation by 5 years.

  • Number of confirmed MR4 and MR4.5. [ Time Frame: After 2 years from study entry. ] [ Designated as safety issue: No ]
    The rate of confirmed MR4 and MR4.5 by 24 months.

  • Number of confirmed MR4 and MR4.5. [ Time Frame: After 60 months from study entry. ] [ Designated as safety issue: No ]
    The rate of confirmed MR4 and MR4.5 by 60 months.

  • Number of stable MR4 and MR4.5 and characteristics. [ Time Frame: After 60 months from study entry. ] [ Designated as safety issue: No ]
    The stability of MR4 and MR4.5.

  • Number of Complete Cytogenetic Responses (CCgR) [ Time Frame: After one year from study entry. ] [ Designated as safety issue: No ]
    The rate of Complete Cytogenetic Response (CCgR) at 1 year.

  • Number of Major Molecular Response (MMR). [ Time Frame: After one year from study entry. ] [ Designated as safety issue: No ]
    The rate of Major Molecular Response (MMR) at 1 year.

  • Number of days to response (CCgR, MMR, MR4, MR4.5). [ Time Frame: After 4 years from study entry. ] [ Designated as safety issue: No ]
    The median time to response and the overall estimated probability of response (CCgR, MMR, MR4, MR4.5).

  • Number of overal surviving patients [ Time Frame: After five years from study entry. ] [ Designated as safety issue: No ]
  • Number of progression-free survival patients. [ Time Frame: After five years from study entry. ] [ Designated as safety issue: No ]
  • Number of failure-free survival patients. [ Time Frame: After five years from study entry. ] [ Designated as safety issue: No ]
  • Number of event-free survival patients. [ Time Frame: After five years from study entry. ] [ Designated as safety issue: No ]
  • Number of responses [ Time Frame: After 7 years from study entry. ] [ Designated as safety issue: No ]
    Overall responses and long-term outcome according to baseline prognostic factors (including: Sokal score34, Euro score35 and EUTOS score36; presence of additional chromosomal abnormalities in Ph+ cells; BCR-ABL transcript type; comorbidity score index).

  • Number of responses according to BCR-ABL transcript levels. [ Time Frame: After 3 and 6 months from study entry. ] [ Designated as safety issue: No ]
    Overall responses and long-term outcome according to BCR-ABL transcript levels and CgR at 3 months and at 6 months.

  • Number of patients with fasting glucose modifications. [ Time Frame: After 24 months from study entry. ] [ Designated as safety issue: No ]
    Fasting glucose modifications (diabetic and normo-glycemic patients) and HbA1C modifications (diabetic patients only) during the first 24 months.

  • Number of patients with modifications of body mass index during treatment compared to baseline. [ Time Frame: After 7 years from study entry. ] [ Designated as safety issue: No ]
    Modifications of body mass index during treatment compared to baseline.

  • Number of patients with modifications of serum lipids during treatment compared to baseline. [ Time Frame: After 7 years from study entry. ] [ Designated as safety issue: No ]
    Modifications of serum lipids during treatment compared to baseline.

  • Patient reported quality of life. [ Time Frame: At 3, 6, 9, 12, 18, 24 months from study entry. ] [ Designated as safety issue: No ]
  • Number of adverse events. [ Time Frame: At 3, 6, 9, 12, 18, 24 months from study entry. ] [ Designated as safety issue: No ]

Estimated Enrollment: 133
Study Start Date: January 2014
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
CML patients Behavioral: Dasatinib discontinuation
Treatment decision is at the discretion of the investigator and must not be made on the basis of this observational study. Patients should have their treatment initiated in accordance with the summary of product characteristics.

Detailed Description:

The primary objective is to describe, in the clinical practice, the rate of events leading to permanent discontinuation after 2 years of treatment with dasatinib as frontline therapy in newly diagnosed CML patients. Imatinib mesylate, a protein tyrosine kinase inhibitor (TKI) targeting BCR-ABL, has become in the last decade the standard of care for Chronic Myeloid Leukaemia (CML) in chronic phase (CP)1-3. Dasatinib is a second generation TKI, effective in imatinib-resistant and imatinib-intolerant patients, which demonstrated superior efficacy to imatinib in early CP BCR-ABL+ CML patients 4,6,7. Most data on second generation TKIs are from company-sponsored studies, generally implemented in selected referral centres. The long-term outcome is still unknown. The high rate of study discontinuation observed within the phase 3 study may influence the mid-term and the long-term data interpretation6,7. A long-term post-marketing surveillance in large independent trial is extremely important to confirm the feasibility of a frontline treatment with the second generation TKI dasatinib and to evaluate the efficacy in a nationwide experience. Moreover, obtaining a deep molecular response is extremely relevant in order to consider TKIs discontinuation. This condition is known as "Complete Molecular Response" (CMR) and is further defined according to the sensitivity achieved (for the definition see the "Criteria of evaluation" section). As far as treatment discontinuation, two experiences have been published so far, aimed at evaluating the persistence of the CMR after imatinib discontinuation. The first was a pilot study32 where 12 patients were included. These 12 patients discontinued imatinib after at least 2 years of CMR (median duration of negativity, 32 months). Six patients displayed a molecular relapse with a detectable BCR-ABL transcript at 1, 2, 3, 4, and 5 months. Imatinib was then reintroduced and led to a novel molecular response. Six other patients (50%) still have an undetectable level of BCR-ABL transcript after a median follow-up of 18 months (range, 9-24 months). The results of this pilot trial have been confirmed and extended in a second trial, the STIM trial33: 100 patients were enrolled, median follow-up 17 months, 69 patients with at least 12 months follow-up: 42 (61%) of these 69 patients relapsed (40 before 6 months, one patient at month 7, and one at month 19). At 12 months, the probability of persistent CMR for these 69 patients was 41% (95% CI 29-52). All patients who relapsed responded to reintroduction of imatinib. An increase of the CMR rate could possibly translate in a higher proportion of patients candidate to stopping anti-CML treatment, with higher probability of remaining disease-free in the long term. Interestingly, dasatinib was able to induce higher 36-month cumulative MR4 and MR4.5 rates than imatinib7. The advantages of this possible future scenario could be: first, the possibility of treatment discontinuation at least in patients with chronic clinical adverse events; second, a potential reduction of the costs of TKI treatment (after the introduction of TKI, the costs of CML treatment is increasing year by year, with the increasing prevalence of CML patients).

In summary, 1) Most data on second generation TKIs are from company-sponsored studies; 2) The high rate of study discontinuation observed within the phase III study may influence the data interpretation; 3) A long-term post-marketing surveillance in large independent trial is extremely important to confirm the efficacy in a nationwide experience; 4) The persistence of CMR after TKI discontinuation have been described in selected patients with "deep" molecular response; 5) A stable CMR is a pre-requisite for treatment discontinuation; 6) A detailed description of the kinetic of the molecular response, potentially related to a subsequent treatment discontinuation, will be done.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

This is a multicentre, observational, prospective study of newly diagnosed chronic phase CML patients treated frontline with Dasatinib 100 mg QD.

Criteria

Inclusion Criteria:

  • Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL+ CML; Age 18 years;
  • Early chronic phase, less than 6 months from diagnosis. Prior treatment with Hydroxyurea or Anagrelide is allowed;
  • Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedures.

Exclusion Criteria:

  • Prior treatment with any protein tyrosin-kinase inhibitor (TKI) or interferon;
  • Recommendations and precautions before allocating a new CML case to dasatinib are fully described in the prescribing information.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761890

Contacts
Contact: Paola Fazi, Dr. p.fazi@gimema.it
Contact: Enrico Crea e.crea@gimema.it

Locations
Italy
Centro Oncologico Basilicata Not yet recruiting
Rionero in Vulture, Potenza, Italy
Contact: Pellegrino Musto, MD, PhD         
Principal Investigator: Pellegrino MUSTO, Pr.         
Sub-Investigator: Giuseppe Pietrantuono, Dr.         
S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo Not yet recruiting
Alessandria, Italy
Contact: Massimo Pini         
Sub-Investigator: Gioacchino Catania         
Principal Investigator: Massimo Pini         
Azienda Ospedaliera - Nuovo Ospedale "Torrette" Recruiting
Ancona, Italy
Contact: Serena Rupoli         
Principal Investigator: Serena Rupoli         
Sub-Investigator: Anna Rita         
U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno Not yet recruiting
Ascoli, Italy
Contact: Catia Bigazzi         
Principal Investigator: Catia Bigazzi         
Az.Ospedaliera S.G.Moscati Not yet recruiting
Avellino, Italy
Contact: Fausto Palmieri         
Principal Investigator: Fausto Palmieri         
Sub-Investigator: Antonio Volpe         
UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro Not yet recruiting
Bari, Italy
Contact: Giorina Specchia         
Principal Investigator: Giorgina Specchia         
Sub-Investigator: Antonella Russo         
Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi Not yet recruiting
Bologna, Italy, 40138
Contact: Gianantonio Rosti, Dr.       gianantonio.rosti@unibo.it   
Principal Investigator: Gianantonio Rosti, Dr.         
U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche Not yet recruiting
Campobasso, Italy
Contact: Sergio Storti         
Principal Investigator: Sergio Storti         
Sub-Investigator: Cristiana Gasbarrino, Dr.         
US Dipartimentale - Centro per le malattie del sangue - Ospedale Civile - S.Giacomo Not yet recruiting
Castelfranco Veneto, Italy
Contact: Giuseppe Tagariello, Dr.         
Principal Investigator: Giuseppe Tagariello, Dr.         
Sub-Investigator: Roberto Sartori, Dr.         
Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto" Not yet recruiting
Catania, Italy
Contact: Fabio Stagno         
Principal Investigator: Fabio Stagno         
Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi Not yet recruiting
Ferrara, Italy
Contact: Antonio Cuneo         
Principal Investigator: Antonio Cuneo         
Sub-Investigator: Francesco Cavazzini         
Azienda Ospedaliera di Firenze Not yet recruiting
Firenze, Italy, 50011
Contact: Alberto BOSI, Pr.         
Principal Investigator: Alberto BOSI, Pr.         
Sub-Investigator: Antonella Gozzini, Dr.         
Centro Aziendale di Ematologia ASL N. 6 Not yet recruiting
Livorno, Italy
Contact: Enrico CAPOCHIANI    0586223111    e.capochiani@nord.usl6.toscana.it   
Principal Investigator: Enrico Capochiani, MD         
Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" Not yet recruiting
Messina, Italy
Contact: Maura Brugiatelli         
Principal Investigator: Maura Brugiatelli         
Sub-Investigator: Laura Nocilli         
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina Not yet recruiting
Messina, Italy
Contact: Caterina Musolino         
Principal Investigator: Caterina Musolino         
Sub-Investigator: Alessandro Allegra         
Ospedale San Gennaro - ASL Napoli 1 Not yet recruiting
Napoli, Italy
Contact: Lucia Mastrullo         
Principal Investigator: Lucia Mastrullo         
Sub-Investigator: Maria Rosaria         
zienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia Not yet recruiting
Napoli, Italy
Contact: Fabrizio Pane         
Principal Investigator: Fabrizio Pane         
Sub-Investigator: Luigia Luciano         
Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2 Not yet recruiting
Orbassano, Italy
Contact: Giovanna Rege         
Principal Investigator: Giovanna Rege         
Sub-Investigator: Carmen Fava         
zienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia Not yet recruiting
Palermo, Italy
Contact: Diamante Turri         
Principal Investigator: Diamante Turri         
La Maddalena Casa di Cura di Alta Specialità Dipartimento Oncologico di III Livello Not yet recruiting
Palermo, Italy
Contact: Maurizio Musso         
Principal Investigator: Maurizio Musso         
Sub-Investigator: Ferdinando Porretto         
Cattedra di Ematologia CTMO Università degli Studi di Parma Not yet recruiting
Parma, Italy
Contact: Monica Crugnola         
Principal Investigator: Monica Crugnola         
Sub-Investigator: Franco Aversa         
U.O. Ematologia Clinica - Azienda USL di Pescara Not yet recruiting
Pescara, Italy
Contact: Roberto Di Lorenzo         
Principal Investigator: Roberto Di Lorenzo         
Sub-Investigator: Giuseppina Ricciuti         
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza Not yet recruiting
Piacenza, Italy
Contact: Daniele Vallisa, Dr.         
Principal Investigator: Daniele Vallisa, Dr.         
Sub-Investigator: Elena Trabacchi, Dr.         
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli" Not yet recruiting
Reggio Calabria, Italy
Contact: Francesco Nobile         
Principal Investigator: Francesco Nobile         
Sub-Investigator: Bruno Martino         
Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova Not yet recruiting
Reggio Emilia, Italy
Contact: Paolo Avanzini         
Principal Investigator: Paolo Avanzini         
Sub-Investigator: Isabella Capodanno         
Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia Not yet recruiting
Roma, Italy
Contact: Enrico Montefusco         
Principal Investigator: Enrico Montefusco         
Sub-Investigator: Raffaele Porrini         
Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo Not yet recruiting
Roma, Italy
Contact: Leonardo Pacilli         
Principal Investigator: Leonardo Pacilli         
U.O.C. Ematologia - Ospedale S.Eugenio Not yet recruiting
Roma, Italy
Contact: Elisabetta Abruzzese         
Principal Investigator: Elisabetta Abruzzese         
Sub-Investigator: Monika Trawinska         
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena Not yet recruiting
Roma, Italy
Contact: Atelda Romano, Dr.         
Principal Investigator: Atelda Romano, Dr.         
Sub-Investigator: Laura Nocilli, Dr.         
Complesso Ospedaliero S. Giovanni Addolorata Not yet recruiting
Roma, Italy
Contact: Michele Cedrone, Dr.         
Sub-Investigator: Barbara Anaclerico, Dr.         
Principal Investigator: Michele Cedrone, Dr.         
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli Not yet recruiting
Roma, Italy
Contact: Simona Sica         
Principal Investigator: Simona Sica         
Sub-Investigator: Federica Sorà         
Rotondo Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza Not yet recruiting
S. G. Rotondo, Italy
Contact: Nicola Cascavilla         
Principal Investigator: Nicola Cascavilla         
Sub-Investigator: Antonietta Pia         
U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte" Not yet recruiting
Siena, Italy
Contact: Monica Bocchia         
Principal Investigator: Monica Bocchia         
Sub-Investigator: Lara Aprile         
Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista Not yet recruiting
Torino, Italy
Contact: Patrizia Pregno         
Principal Investigator: Patrizia Pregno         
Sub-Investigator: Paola Riccomagno         
Clinica Ematologica - Policlinico Universitario Not yet recruiting
Udine, Italy
Contact: Mario Tiribelli         
Principal Investigator: Mario Tiribelli         
Sub-Investigator: Luciana Marin         
Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi Not yet recruiting
Verona, Italy
Contact: Giovanni Pizzolo         
Principal Investigator: Giovanni Pizzolo         
Sub-Investigator: Massimiliano Bonifacio         
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
  More Information

No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT01761890     History of Changes
Other Study ID Numbers: CML1113, RSO ID 714
Study First Received: January 3, 2013
Last Updated: January 30, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Chronic Myeloid Leukemia
Early phase
CML
Dasatinib

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014