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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01535391
Other study ID # CML0811
Secondary ID 2011-002787-25
Status Completed
Phase Phase 3
First received
Last updated
Start date January 2012
Est. completion date April 27, 2018

Study information

Verified date August 2018
Source Gruppo Italiano Malattie EMatologiche dell'Adulto
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally twice daily for 24 months and indefinitely if it is in the interest of the patient.

The primary objective of the trial is to evaluate the efficacy of nilotinib, 300 mg twice daily with dose increase to 400 mg twice daily in case of suboptimal response or failure (excluding patients who will fail for progression to ABP), in a population of patients with Ph-positive, BCR-ABL positive CML in early CP.


Description:

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choice of the treatment will be up to the physician).

Study duration is estimated in 6 years, 1 year of estimated enrollment, 2 years therapy duration. Thereafter, information on course and survival is due for other 3 years.

The main data analysis will be performed when all patients will complete 24 months of treatment (or discontinued earlier). Safety and tolerability profile will be assessed by collecting hematologic and non-hematologic adverse events, laboratory examinations and ECG data. The molecular response will be assessed using the GIMEMA standardized molecular laboratories (Labnet network).


Recruitment information / eligibility

Status Completed
Enrollment 109
Est. completion date April 27, 2018
Est. primary completion date November 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Age = 18

- Male or female patients with diagnosis of Ph+ and/or BCR-ABL+ CML

- Early chronic phase (within 6 months from diagnosis)

- Pretreatment with Hydroxyurea or Anagrelide for a duration of up to 3 months and/or pretreatment with Imatinib for up to 30 days are permitted

- Normal serum levels of potassium, magnesium, phosphorus, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements prior to the first dose of study medication

- Written informed consent prior to any study procedures being performed

- AST and ALT = 2.5 x ULN or = 5.0 x ULN if considered due to leukaemia

- Alkaline phosphatase = 2.5 x ULN unless considered due to leukaemia

- Total direct bilirubin = 1.5 x ULN, except know Mb. Gilbert

- Serum creatinine = 1.5 x ULN

Exclusion Criteria:

- Known impaired cardiac function, including any of the following:

- LVEF < 45%

- Complete left bundle branch block

- Right bundle branch block plus left anterior hemiblock, bifascicular block

- Use of a ventricular-paced pacemaker

- Congenital long QT syndrome

- History of or presence of clinically significant ventricular or atrial tachyarrhythmias

- Clinically significant resting bradycardia (<50 beats per minute)

- QTc>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before Nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion.

- Myocardial infarction within 12 months prior to starting study drugs

- Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)

- Serum lipase and amylase > 1.5 x ULN (upper limit of normal) or history of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis

- Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol

- Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)

- Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm)

- Concomitant medications known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9,andCYP2C8:link for complete list: http://medicine.iupui.edu/flockhart/table.html..

- Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

- Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of nilotinib).

- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.

- Patients unwilling or unable to comply with the protocol

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Nilotinib
Administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choise of the treatment will be up to the physician).

Locations

Country Name City State
Italy Azienda Ospedaliera Nuovo Ospedale "Torrette" Ancona
Italy S.G. Moscati Hospital Avellino
Italy Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi Bologna
Italy USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia Brescia
Italy Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto" Catania
Italy Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia Catanzaro
Italy Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna Ferrara
Italy Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria Foggia
Italy Clinica Ematologica - DiMI - Università degli Studi di Genova Genova
Italy Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino" Genova
Italy U.O. di Ematologia- Ospedale dell'Angelo - Mestre Mestre
Italy U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele Milano
Italy Centro Oncologico Modenese - Dipartimento di Oncoematologia Modena
Italy Università degli Studi di Padova - Ematologia ed Immunologia Clinica Padova
Italy Azienda Ospedaliera Universitaria - Policlinico Paolo Giaccone Palermo
Italy Ospedale Cervello Palermo
Italy Div. di Ematologia di Muraglia -CTMO Ospedale San Salvatore Pesaro
Italy Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza Piacenza
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 IRCCS Centro di riferimento Oncologico di Basilicata Rionero in Vulture
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 U.O.C. Ematologia Ospedale S. Eugenio Roma
Italy Università degli Studi Policlinico di Tor Vergata Roma
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 U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati Taranto
Italy SCDO Ematologia 2 AOU S.Giovanni Battista Torino
Italy Azienda USL 9 Treviso - 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

Sponsors (1)

Lead Sponsor Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Complete molecular response To assess the complete molecular response (CMR4) rate at 24 months of treatment. For the purpose of this protocol, CMR is defined as a negative results of quantitative RT-PCR for BCR-ABL transcripts in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000, that corresponds to at least a 4-log reduction (hence, CMR4) At 24 months of treatment
Secondary Toxicity Number of toxic events At three years from study entry
Secondary Compliance Number of fully compliant patients and number of patients who do not comply with treatment At 3 years from study entry
Secondary The complete cytogenetic response (CCgR) rate At 3, 6, 12, 18 and 24 months from study entry
Secondary The rate and the degree of molecular response At 3, 6, 12, 18 and 24 months from study entry
Secondary The time to CCgR, the time to MMR and the time to CMR baseline
Secondary Overall Survival (OS) From the date of the first nilotinib dose to death At three years from study entry
Secondary Progression Free Survival (PFS) From the date of the first nilotinib dose to progression to AP or BP or death At three years from study entry
Secondary Failure Free Survival (FFS) From the date of the first nilotinib dose to failure* or progression or death At three years from study entry
Secondary Event Free Survival (EFS) From the date of the first nilotinib to any event. Including treatment discontinuation for adverse events, failure, progression to AP or BP, or death, whichever comes first. At three years from study entry
Secondary Patient-reported quality of life (QoL) At baseline and then at 3, 6, 12, 18 and 24 months
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