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

NCT ID: NCT01761890

Last Updated: 2022-01-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 147 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-28
• Study Completion Date: 2022-12-31

Brief Summary

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.

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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

CML patients

Dasatinib discontinuation

Intervention Type: BEHAVIORAL

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.

Interventions

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.

Intervention Type: BEHAVIORAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Baccarani, Pr.

Role: STUDY_CHAIR

Orsola Malpighi, Bologna

Locations

Centro Oncologico Basilicata

Rionero in Vulture, Potenza, Italy

S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Azienda Ospedaliera - Nuovo Ospedale "Torrette"

Ancona, , Italy

U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno

Ascoli Piceno, , Italy

Az.Ospedaliera S.G.Moscati

Avellino, , Italy

UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

Bari, , Italy

Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

Bologna, , Italy

U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche

Campobasso, , Italy

US Dipartimentale - Centro per le malattie del sangue - Ospedale Civile - S.Giacomo

Castelfranco Veneto, , Italy

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, , Italy

Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi

Ferrara, , Italy

Azienda Ospedaliera di Firenze

Florence, , Italy

Centro Aziendale di Ematologia ASL N. 6

Livorno, , Italy

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, , Italy

Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano

Milan, , Italy

Ospedale San Gennaro - ASL Napoli 1

Napoli, , Italy

zienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, , Italy

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2

Orbassano, , Italy

La Maddalena Casa di Cura di Alta Specialità Dipartimento Oncologico di III Livello

Palermo, , Italy

zienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Palermo, , Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, , Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

Piacenza, , Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, , Italy

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia

Roma, , Italy

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo

Roma, , Italy

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

Roma, , Italy

U.O.C. Ematologia - Ospedale S.Eugenio

Roma, , Italy

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Rotondo Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista

Torino, , Italy

Clinica Ematologica - Policlinico Universitario

Udine, , Italy

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, , Italy

Countries

Italy

Related Links

http://www.gimema.it

GIMEMA Foundation

Other Identifiers

RSO ID 714

Identifier Type: OTHER

Identifier Source: secondary_id

CML1113

Identifier Type: -

Identifier Source: org_study_id