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Chronic Myeloid LeukemiaPhase 3CML0811NCT01535391

Nilotinib in PH+, BCR-, ABL+ CML Patients

A Phase 3 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 34 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia
What is being tested?
Nilotinib
Type of treatment
Pill or oral medicine
How many people
109 participants
Where
34 sitesItaly
Study dates
Jan 2012to 27 Apr 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

Italy34 sites

  • Azienda Ospedaliera Nuovo Ospedale "Torrette"

    Ancona

  • S.G. Moscati Hospital

    Avellino

  • Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

    Bologna, 40138

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

    Brescia, 25123

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

    Catania

  • Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia

    Catanzaro

  • Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna

    Ferrara

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

    Foggia

  • Clinica Ematologica - DiMI - Università degli Studi di Genova

    Genova

  • Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"

    Genova

  • U.O. di Ematologia- Ospedale dell'Angelo - Mestre

    Mestre

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

    Milan

  • Centro Oncologico Modenese - Dipartimento di Oncoematologia

    Modena

  • Università degli Studi di Padova - Ematologia ed Immunologia Clinica

    Padova

  • Ospedale Cervello

    Palermo, 90146

  • Azienda Ospedaliera Universitaria - Policlinico Paolo Giaccone

    Palermo

  • Div. di Ematologia di Muraglia -CTMO Ospedale San Salvatore

    Pesaro

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

    Piacenza

  • Dipartimento Oncologico - Ospedale S.Maria delle Croci

    Ravenna

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

    Reggio Calabria

  • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

    Reggio Emilia

  • Ospedale "Infermi"

    Rimini

  • IRCCS Centro di riferimento Oncologico di Basilicata

    Rionero in Vulture

  • Complesso Ospedaliero S. Giovanni Addolorata

    Roma

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

    Roma

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

    Roma

  • Università degli Studi Policlinico di Tor Vergata

    Roma

  • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

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

    Siena

  • U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati

    Taranto

  • SCDO Ematologia 2 AOU S.Giovanni Battista

    Torino

  • Azienda USL 9 Treviso - U.O. di Ematologia

    Treviso, 31100

  • Clinica Ematologica - Policlinico Universitario

    Udine

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

    Verona

Other trials in Italy

About this study

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

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.

Read the detailed 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).

Being tested
Nilotinib
Keywords
Chronic Myeloid Leukemia,, Nilotinib,, Philadelphia positive,, BCR-ABL+, Early chronic phase
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NilotinibDrug

    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).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: At 24 months of treatment

Secondary outcomes (10)

  1. Toxicity

    Number of toxic events

    Measured: At three years from study entry

  2. Compliance

    Number of fully compliant patients and number of patients who do not comply with treatment

    Measured: At 3 years from study entry

  3. The complete cytogenetic response (CCgR) rate

    Measured: At 3, 6, 12, 18 and 24 months from study entry

  4. The rate and the degree of molecular response

    Measured: At 3, 6, 12, 18 and 24 months from study entry

  5. The time to CCgR, the time to MMR and the time to CMR

    Measured: baseline

  6. Overall Survival (OS)

    From the date of the first nilotinib dose to death

    Measured: At three years from study entry

  7. Progression Free Survival (PFS)

    From the date of the first nilotinib dose to progression to AP or BP or death

    Measured: At three years from study entry

  8. Failure Free Survival (FFS)

    From the date of the first nilotinib dose to failure* or progression or death

    Measured: At three years from study entry

  9. 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.

    Measured: At three years from study entry

  10. Patient-reported quality of life (QoL)

    Measured: At baseline and then at 3, 6, 12, 18 and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionNov 2014
  4. Study completion27 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
109 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01535391
Sponsor's protocol ID
CML0811
Other IDs
2011-002787-25
Acronym
CML0811
Status last verified
Aug 2018
First submitted
9 Feb 2012
Last updated
6 Aug 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Castagnetti F, Breccia M, Gugliotta G, Martino B, D'Adda M, Stagno F, Carella AM, Avanzini P, Tiribelli M, Trabacchi E, Visani G, Gobbi M, Salvucci M, Levato L, Binotto G, Capalbo SF, Bochicchio MT, Soverini S, Cavo M, Martinelli G, Alimena G, Pane F, Saglio G, Rosti G, Baccarani M; GIMEMA CML Working Party. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients. Haematologica. 2016 Oct;101(10):1200-1207. doi: 10.3324/haematol.2016.144949. Epub 2016 Jul 28.

    PubMed 27470600

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 34 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete molecular response (time frame: At 24 months of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01535391, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2018.

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