Nilotinib as First-line Treatment of Ph+ CML in Early Chronic Phase (CML0307)
Treating Ph pos CML with Imatinib is very effective since the majority of the patients achieve a complete cytogenetic response and a major molecular response and are alive and progression-free after 5 years. However, the great majority of responding patients are not leukemia-free and may be at risk of progression, molecular, cytogenetic and clinical, at any time. In case of disease progression due to Imatinib failure, nilotinib has been found to be very effective, as expected from the preclinical profile of the drug, that is much more potent against BCR-ABL and inhibits nearly all the imatinib-resistant BCR-ABL mutants. For these reasons, nilotinib is going to be registered for the treatment of imatinib-resistant CMl patients. For the same reasons, nilotinib is expected to be more efficient than imatinib also front-line, based on the principle that we should aim at preventing the emergence of resistance better that at treating resistance once it has emerged. This expectation can be tested safely, because the "toxicity profile" of Nilotinib may be even more convenient than that of Imatinib, due to the lower frequency of edema and fluid retention.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Protein Tyrosine Kinase Inhibitor Nilotinib as First-line Treatment of Ph+ Chronic Myeloid Leucemia (CML) in Early Chronic Phase: a Phase II Exploratory, Multicenter Study. GIMEMA Protocol CML 0307. EUDRACT 2007-000597-22.|
- Complete cytogenetic response (CCgR ) rate [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
- The complete and the partial cytogenetic response rate [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
- The major molecular response (MMR) rate [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
- The kinetics of haematologic, cytogenetic and molecular response to AMN107 [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
- The development of bcr-abl mutation during the treatment with AMN107 (number and type) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
- The safety and tolerability of nilotinib treatment at the dose of 300 mg b.i.d [ Time Frame: At 1 year ] [ Designated as safety issue: Yes ]
- To describe any SAE [ Time Frame: At 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2007|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Phase II, Prospective, multicentric, non randomized, open label
The primary objective of the trial is to investigate the cytogenetic and molecular effects of the protein tyrosine kinase (PTK) inhibitor nilotinib in the treatment of early chronic phase Ph+ CML.
The secondary objectives are:
To investigate in early CP Ph+ CML patients treated with nilotinib the clinical and the hematologic effects, the effect on bcr/abl point mutations, the kinetic of the response, the toxicity, the compliance to treatment and the dose density.
This study is an open-label, multicenter, exploratory, Phase II study of nilotinib administered orally twice daily for one year. For the patients who will benefit an extension to 4 years is planned.
Visit Schedule and Assessments:
A visit with blood counts and differential and serum chemistry is due baseline, every 15 days for 3 months, hence every 30 days.
An ECG is due baseline, after 15 and 30 days, hence at 60, 90, 150, 240 and 360 days.
An echocardiogram is due baseline and at end-of-study (360 days) or early withdrawal.
A bone marrow aspirate is due baseline (cytology, cytogenetics and quantitative molecular biology), after 3 and 6 months (cytology and cytogenetics) and after 12 months (cytology, cytogenetics, quantitative molecular biology and mutational analysis).
A peripheral blood sample is due baseline, at 30, 60, 90, 180, 270 and 360 days for quantitative molecular biology.
After the end of the study (i.e. after one year) clinical, cytogenetic and molecular data are due every 6 months.
Bone marrow and peripheral blood cells will be collected before, during and at the end of the study, stored at the central lab in Bologna and used for molecular assays that are listed in details in the protocol, with the exclusion of any test allowing the identification of patients genotype. The samples are kept for a minimum of 10 years and can be destroyed upon patient request. A specific consent form to the sample storage will be submitted to the patients.
|Dipartimento Area Medica P.O.|
|Ascoli Piceno, Italy, 63100|
|Unità Operativa Ematologica - Università degli Studi di Bari|
|Bari, Italy, 70124|
|Bergamo, Italy, 24100|
|stituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi|
|Azienda Spedali Civili|
|Brescia, Italy, 25100|
|Sezione di Ematologia e Trapianti Spedali Civili|
|Brescia, Italy, 21125|
|ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO|
|Catania, Italy, 95124|
|Azienda Ospedaliera Pugliese Ciaccio|
|Catanzaro, Italy, 88100|
|Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna|
|Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia|
|Ospedale S. Luigi Gonzaga|
|Orbassano, Italy, 10043|
|La Maddalena Casa di Cura di Alta Specialità Dipartimento Oncologico di III Livello|
|Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza|
|Ospedale S.Maria delle Croci|
|Ravenna, Italy, 48100|
|Calabria Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"|
|Reggio Calabria, Italy|
|Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia|
|Complesso Ospedaliero S. Giovanni Addolorata|
|Roma, Italy, 00184|
|Università La Cattolica del Sacro Cuore|
|Roma, Italy, 00168|
|U.O. Ematologia, Azienda Ospedaliera Universitaria Senese|
|Siena, Italy, 53100|
|Policlinico Universitario - Clinica Ematologia|
|Udine, Italy, 33100|
|Policlinico G.B. Rossi|
|Verona, Italy, 37134|
|Principal Investigator:||Michele BACCARANI||Azienda Ospedaliera Universitaria -Policlincio S. Orsola-Malpighi|