Nilotinib in PH+, BCR-, ABL+ CML Patients (CML0811)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01535391
First received: February 9, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Nilotinib
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy 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+, BCR-, ABL+ Chronic Myeloid Leukemia (CML) in Early Chronic Phase: a Phase IIIb, Multicenter Study to Assess the Complete Molecular Response

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete molecular response [ Time Frame: At 24 months of treatment ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Toxicity [ Time Frame: At three years from study entry ] [ Designated as safety issue: Yes ]
    Number of toxic events

  • Compliance [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]
    Number of fully compliant patients and number of patients who do not comply with treatment

  • The complete cytogenetic response (CCgR) rate [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ] [ Designated as safety issue: No ]
  • The rate and the degree of molecular response [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ] [ Designated as safety issue: No ]
  • The time to CCgR, the time to MMR and the time to CMR [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
    From the date of the first nilotinib dose to death

  • Progression Free Survival (PFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
    From the date of the first nilotinib dose to progression to AP or BP or death

  • Failure Free Survival (FFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
    From the date of the first nilotinib dose to failure* or progression or death

  • Event Free Survival (EFS) [ Time Frame: At three years from study entry ] [ Designated as safety issue: No ]
    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.

  • Patient-reported quality of life (QoL) [ Time Frame: At baseline and then at 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 109
Study Start Date: January 2012
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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).
Detailed Description:

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administred 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).

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01535391

Locations
Italy
Azienda Ospedaliera Nuovo Ospedale "Torrette"
Ancona, Italy
S.G. Moscati Hospital
Avellino, Italy
Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
Bologna, Italy, 40138
USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia
Brescia, Italy, 25123
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
Ospedale Cervello
Palermo, Italy, 90146
Azienda Ospedaliera Universitaria - Policlinico Paolo Giaccone
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
U.O.C. Ematologia Ospedale S. Eugenio
Roma, Italy
Università degli Studi Policlinico di Tor Vergata
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
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
S. G. 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, 31100
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
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: NCT01535391     History of Changes
Other Study ID Numbers: CML0811, 2011-002787-25
Study First Received: February 9, 2012
Last Updated: May 12, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Chronic Myeloid Leukemia,
Nilotinib,
Philadelphia positive,
BCR-ABL+
Early chronic phase

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on July 20, 2014