Front-line Nilotinib Treatment of BCR-ABL+ Chronic Myeloid Leukaemia in Chronic Phase

NCT ID: NCT01699217

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 129 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-06-21
• Study Completion Date: 2023-12-28

Brief Summary

The GIMEMA CML Working Party promotes a multicentre, observational, prospective study of CML patients treated frontline with NIL. Patients will be followed for 5 years. This study will help the definition of guidelines for the treatment of CML patients in early CP.

Detailed Description

The primary objective of the study is to describe the stability of molecular response with NIL as frontline therapy in newly diagnosed, unselected, CP CML patients, in an independent, investigator-initiated observational study. Imatinib mesylate (IM), 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)1,2. Nilotinib (NIL) is a second generation TKI, effective in IM-resistant and IM-intolerant patients, which demonstrated superior efficacy to IM in early CP BCR-ABL+ CML patients3. Currently, the most important target of the treatment of CML with TKIs is the major molecular response (MMR), defined as a ≥ 3 log reduction in BCR-ABL/ABL transcript level, marker of better long-term outcome. With imatinib therapy, achieving a MMR correlates with an improved probability of a durable cytogenetic remission30. Results from IRIS suggest that a MMR after 12 months of imatinib therapy may be a marker of stable response. Further on, the IRIS study showed that patients with a MMR after 12 months of therapy had a significantly better probability of disease-free survival compared with those in complete cytogenetic remission, but not in MMR31. Moreover, obtaining an undetectable BCR-ABL transcript level 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, 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. 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). Standardized molecular monitoring has become widely available in Europe through the efforts of EUTOS cooperation19 and now allows for the generation of comparable data on the residual disease using recalculation on the international scale despite these data being analyzed in many different laboratories. These advances in the standardization of molecular responses and the improvement of targeted therapy have allowed for comparable response assessment across Italian Centres and early treatment optimization of patients.

In summary, 1) monitoring of molecular response and of deep and sustained molecular response, provides a straightforward opportunity to assess patients' response and possible prognosis in the use of targeted therapy. 2) Most data on second generation TKIs are from company-sponsored studies generally implemented in selected referral centres. 3) The detailed description of the kinetic of the molecular response and, particularly, the rate of stable MR4, potentially related in turn with a subsequent treatment discontinuation, within the frame of a long-term post-marketing surveillance observational trial offered to all eligible patients followed at a nation-wide, independent multicentre group is the core distinctive feature of this observational trial.

Conditions

Chronic Phase Philadelphia Positive; BCR-ABL Positive; Chronic Myeloid Leukaemia

Study Design

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

Eligibility Criteria

Inclusion Criteria

• Age: >=18 years;
• Patients with chronic phase Ph+ and/or BCR-ABL+ CML, newly diagnosed (less than 6 months);
• Prior treatment with Hydroxyurea or Anagrelide is allowed;
• Prior treatment with IM for less than 30 days is allowed;
• Signed written informed const according to ICH/EU/GCP and national local laws.

Exclusion Criteria

• Patients who are pregnant (negative pregnancy test is requested within 2 days before nilotinib start) or breast feeding, or adults of reproductive potential not employing an effective method of birth control.
• Newly diagnosed Ph+ and/or BCR-ABL+ CML patients in advanced phases (accelerated or blastic phase).
• Prior treatment with nilotinib, dasatinib, or other tyrosine-kinase inhibitors.

• 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

Gianantonio Rosti, Pr.

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology and Oncological Sciences, S.Orsola-Malpighi Hospital, University of Bologna

Locations

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

Alessandria, , Italy

Azienda Ospedaliera Nuovo Ospedale "Torrette"

Ancona, , Italy

Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"

Ascoli Piceno, , Italy

Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

Bari, , Italy

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia

Brescia, , Italy

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO

Cagliari, , 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

ezione di Ematologia C.T.M.O. Istituti Ospitalieri

Cremona, , Italy

Ospedale Santa Croce Divisione di Ematologia Cuneo

Cuneo, , Italy

Policlinico di Careggi, Università delgi studi di Firenze

Florence, , Italy

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria

Foggia, , Italy

Clinica Ematologica - DiMI - Università degli Studi di Genova

Genova, , Italy

IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente

Genova, , Italy

SOC Ematologia e Centro Trasfusionale Ospedale di Ivrea - ASL TO4

Ivrea, , Italy

Divisione di Ematologia Ospedale "Santa Maria Goretti"

Latina, , 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

U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele

Milan, , Italy

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

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

Napoli, , Italy

Ospedale San Gennaro - ASL Napoli 1

Napoli, , Italy

Sez. di Ematologia Clinica Ospedale San Francesco

Nuoro, , Italy

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

Orbassano, , Italy

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, , Italy

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"

Palermo, , Italy

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

Palermo, , Italy

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, , Italy

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, , 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

Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia

Pisa, , Italy

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, , Italy

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

Reggio Calabria, , Italy

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Ospedale "Infermi"

Rimini, , Italy

U.O. di Ematologia - Centro Oncologico Basilicata

Rionero in Vulture, , Italy

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

Roma, , Italy

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"

Roma, , Italy

Segreteria di Ematologia - 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

Azienda Sanitaria Locale Viterbo - Polo Ospedaliero Centrale - Ospedale Di Ronciglione - U.O. di Ematologia

Ronciglione, , Italy

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

SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni

Terni, , 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

Sezione di Ematologia - Med.II Div. Presidio Ospedaliero S. Chiara di Trento

Trento, , Italy

Azienda U.L.S.S.9 - U.O. di Ematologia

Treviso, , 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

Other Identifiers

CML0912

Identifier Type: -

Identifier Source: org_study_id