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Chronic Myeloid LeukemiaPhase 2CML0307NCT00481052

Nilotinib as First-line Treatment of Ph+ CML in Early Chronic Phase

A Phase 2 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 22 sites in Italy.

Completed

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

Official record
Search all trials

Trial summary

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. 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
How many people
74 participants
Where
22 sitesItaly
Study dates
23 Jun 2007to 30 Apr 2018
Phase
Phase 2
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

  • Patients with a cytologic and cytogenetic confirmed diagnosis of Ph+ CML.
  • Age ≥ 18 years old
  • Early CP (within 6 months from diagnosis)
  • No prior treatment with any antileukemic drugs with the exception of Hydroxyurea (HU) and Anagrelide.
  • WHO performance status of ≤ 2
  • Normal serum level of potassium, total calcium corrected for serum albumin, magnesium and phosphorus, or correctable with supplements
Show all 12Show fewer
  • ALT and AST ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia.
  • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukemia.
  • Serum bilirubin ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN
  • Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN.
  • Written informed consent prior to any study procedures being performed.

Who cannot join

  • Impaired cardiac function, including LVEF < 45% as determined by MUGA scan or echocardiogram, uncontrolled congestive heart failure, uncontrolled hypertension
  • History of myocardial infarction within three months, or uncontrolled angina pectoris.
  • Significant electric heart abnormalities, including history or presence of significant ventricular or atrial tachyarrhythmias, congenital long QT syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula).
  • Patients with ventricular pacemakers and clinically significant bradycardias.
  • Patients with heart blocks.
  • History of acute or chronic pancreatitis.
Show all 20Show fewer
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Use of therapeutic coumarin derivates (i.e. warfarin, acenocoumarol, phenprocoumon).
  • Acute or chronic liver or renal disease considered unrelated to leukaemia
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients who are currently receiving treatment with any of the medications listed in Appendix E and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT, with the exception of HU and Anagrelide.
  • Patients who have received any antileukemic agents and treatments, including HSCT, with the exception of HU and Anagrelide.
  • Patients who have received any investigational drug ≤ 4 weeks.
  • 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 adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
  • Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) 1 week prior to starting study drug.
  • Patients who have received immunotherapy 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
  • 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

22 sites in 1 country.

22 sites in 1 country

Italy22 sites

  • Dipartimento Area Medica P.O.

    Ascoli Piceno, 63100

  • Unità Operativa Ematologica - Università degli Studi di Bari

    Bari, 70124

  • Ospedali Riuniti

    Bergamo, 24100

  • stituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

    Bologna

  • Sezione di Ematologia e Trapianti Spedali Civili

    Brescia, 21125

  • Azienda Spedali Civili

    Brescia, 25100

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

    Cagliari

  • Ospedale Ferrarotto

    Catania, 95124

  • Azienda Ospedaliera Pugliese Ciaccio

    Catanzaro, 88100

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

    Ferrara

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

    Naples

  • Ospedale S. Luigi Gonzaga

    Orbassano, 10043

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

    Palermo

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

    Piacenza

  • Ospedale S.Maria delle Croci

    Ravenna, 48100

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

    Reggio Calabria

  • Università La Cattolica del Sacro Cuore

    Roma, 00168

  • Complesso Ospedaliero S. Giovanni Addolorata

    Roma, 00184

  • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

    Roma

  • U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

    Siena, 53100

  • Policlinico Universitario - Clinica Ematologia

    Udine, 33100

  • Policlinico G.B. Rossi

    Verona, 37134

Other trials in Italy

About this study

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.

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.

Read the detailed description

Study Phase:

Phase II, Prospective, multicentric, non randomized, open label

Objectives:

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.

Study design:

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.

Biologic Monitoring:

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.

Being tested
Nilotinib
Keywords
Adult, CML, Philadelphia positive, Nilotinib, early chronic phase, untreated or treated only with Hydroxyurea or Anagrelide, Chronic Myeloid Leukemia
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

What is being measured

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

  1. Complete cytogenetic response (CCgR ) rate

    Measured: At 1 year

Secondary outcomes (6)

  1. The complete and the partial cytogenetic response rate

    Measured: At 6 months

  2. The major molecular response (MMR) rate

    Measured: At 1 year

  3. The kinetics of haematologic, cytogenetic and molecular response to AMN107

    Measured: At 1 year

  4. The development of bcr-abl mutation during the treatment with AMN107 (number and type)

    Measured: At 1 year

  5. The safety and tolerability of nilotinib treatment at the dose of 300 mg b.i.d

    Measured: At 1 year

  6. To describe any SAE

    Measured: At 1 year

Timeline

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

  1. First posted1 Jun 2007 (estimated)
  2. Study start23 Jun 2007
  3. Primary completion30 Apr 2018
  4. Study completion30 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00481052
Sponsor's protocol ID
CML0307
Acronym
CML0307
Status last verified
Jan 2022
First submitted
31 May 2007
Last updated
18 Jan 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Calabretta B, Perrotti D. The biology of CML blast crisis. Blood. 2004 Jun 1;103(11):4010-22. doi: 10.1182/blood-2003-12-4111. Epub 2004 Feb 24.

    PubMed 14982876

  • Barnes DJ, Melo JV. Management of chronic myeloid leukemia: targets for molecular therapy. Semin Hematol. 2003 Jan;40(1):34-49. doi: 10.1053/shem.2003.50002.

    PubMed 12563610

  • Goldman JM, Melo JV. Chronic myeloid leukemia--advances in biology and new approaches to treatment. N Engl J Med. 2003 Oct 9;349(15):1451-64. doi: 10.1056/NEJMra020777. No abstract available.

    PubMed 14534339

  • Goldman JM, Marin D, Olavarria E, Apperley JF. Clinical decisions for chronic myeloid leukemia in the imatinib era. Semin Hematol. 2003 Apr;40(2 Suppl 2):98-103; discussion 104-13. doi: 10.1053/shem.2003.50049.

    PubMed 12783383

  • Goldman JM, Marin D. Management decisions in chronic myeloid leukemia. Semin Hematol. 2003 Jan;40(1):97-103. doi: 10.1053/shem.2003.50009.

    PubMed 12563616

  • Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood. 2001 Oct 1;98(7):2039-42. doi: 10.1182/blood.v98.7.2039.

    PubMed 11567987

  • Baccarani M, Russo D, Rosti G, Martinelli G. Interferon-alfa for chronic myeloid leukemia. Semin Hematol. 2003 Jan;40(1):22-33. doi: 10.1053/shem.2003.50004.

    PubMed 12563609

  • Martinelli G, Soverini S, Rosti G, Cilloni D, Baccarani M. New tyrosine kinase inhibitors in chronic myeloid leukemia. Haematologica. 2005 Apr;90(4):534-41.

    PubMed 15820950

  • Rosti G, Martinelli G, Bassi S, Amabile M, Trabacchi E, Giannini B, Cilloni D, Izzo B, De Vivo A, Testoni N, Cambrin GR, Bonifazi F, Soverini S, Luatti S, Gottardi E, Alberti D, Pane F, Salvatore F, Saglio G, Baccarani M; Study Committee, Italian Cooperative Study Group for Chronic Myeloid Leukemia; Writing Committee, Italian Cooperative Study Group for Chronic Myeloid Leukemia. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood. 2004 Mar 15;103(6):2284-90. doi: 10.1182/blood-2003-07-2575. Epub 2003 Nov 26.

    PubMed 14645009

  • Gugliotta G, Castagnetti F, Breccia M, Levato L, D'Adda M, Stagno F, Tiribelli M, Salvucci M, Fava C, Martino B, Cedrone M, Bocchia M, Trabacchi E, Cavazzini F, Usala E, Russo Rossi A, Bochicchio MT, Soverini S, Alimena G, Cavo M, Pane F, Martinelli G, Saglio G, Baccarani M, Rosti G; GIMEMA CML Working Party. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia. Haematologica. 2015 Sep;100(9):1146-50. doi: 10.3324/haematol.2015.129221. Epub 2015 Jun 25.

    PubMed 26113419

  • Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G; GIMEMA CML Working Party. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015 Jan;26(1):185-192. doi: 10.1093/annonc/mdu490. Epub 2014 Oct 30.

    PubMed 25361995

  • Lenaerts T, Castagnetti F, Traulsen A, Pacheco JM, Rosti G, Dingli D. Explaining the in vitro and in vivo differences in leukemia therapy. Cell Cycle. 2011 May 15;10(10):1540-4. doi: 10.4161/cc.10.10.15518. Epub 2011 May 15.

    PubMed 21478667

  • Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M; GIMEMA CML Working Party. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.

    PubMed 19822896

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 22 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 12 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 18 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 cytogenetic response (CCgR ) rate (time frame: At 1 year). 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 NCT00481052, which also lists 13 linked publications.

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 18 Jan 2022.

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