Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia (CML0408)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00769327
Recruitment Status : Completed
First Posted : October 9, 2008
Last Update Posted : January 28, 2015
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:

RATIONALE: Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well giving nilotinib together with imatinib mesylate works in treating patients with early chronic phase chronic myelogenous leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Drug: imatinib mesylate Drug: nilotinib Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Genetic: microarray analysis Genetic: mutation analysis Genetic: polymerase chain reaction Genetic: polymorphism analysis Other: laboratory biomarker analysis Phase 2

Detailed Description:



  • To assess the complete cytogenetic response rate at 12 months in patients with Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous leukemia treated with nilotinib and imatinib mesylate.


  • To assess the complete cytogenetic response rate at 6 and 24 months in these patients.
  • To assess the major and complete molecular response rate at 6, 12, and 24 months in these patients.
  • To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months during and for 3 years after study treatment.
  • To assess the rate of failures and the time to failure at 12, 24, and 60 months in these patients.
  • To assess compliance, toxicity, and adverse events in these patients.
  • To understand the relationship between response, gene expression profile, biomarkers, and drug plasma concentrations in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral nilotinib twice daily in months 1-3, 7-9, 13-15, and 19-21 and oral imatinib mesylate once daily in months 4-6, 10-12, 16-18, and 22-24. Treatment continues for 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible to continue oral nilotinib and oral imatinib mesylate for up to another 36 months if it is in the interest of the patient.

Blood samples and bone marrow biopsies are collected periodically for cytogenetic response by chromosome banding analysis and FISH analysis; real-time quantitative PCR mutational analysis and single nucleotide polymorphism analysis of BCR-ABL transcripts; and gene expression profiling and correlative biomarker studies.

After completion of study therapy, patients are followed every 6 months for 3 years and then every 12 months for 5 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.
Study Start Date : February 2009
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Primary Outcome Measures :
  1. Complete cytogenetic response rate [ Time Frame: At 12 months from study entry ]

Secondary Outcome Measures :
  1. Complete cytogenetic response [ Time Frame: At at 6 and 24 months from study entry ]
  2. Major and complete molecular response rate [ Time Frame: At at 6, 12 and 24 months from study entry ]
  3. Development of BCR-ABL kinase domain mutations (number, timing, and type) [ Time Frame: At at 24 months during and for 3 years after study treatment ]
  4. Rate of failures and the time to failure [ Time Frame: At 12, 24, and 60 months from study entry ]
  5. Safety and tolerability [ Time Frame: At 24 months from study entry ]
  6. Frequency and type of adverse events (AE) and severe AE [ Time Frame: At 24 months from study entry ]
  7. Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylate [ Time Frame: At 24 months from study entry ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the following criteria:

    • Early chronic phase disease (< 6 months from diagnosis)
    • Philadelphia chromosome-positive disease
    • BCR-ABL-positive


  • WHO performance status 0-1
  • ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due to leukemia)
  • Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia)
  • Serum bilirubin = 1.5 times ULN
  • Serum creatinine = 1.5 times ULN
  • Serum amylase = 1.5 times ULN
  • Serum lipase = 1.5 times ULN
  • Normal serum levels of the following or correctable with supplements:

    • Potassium
    • Total calcium (corrected for serum albumin)
    • Magnesium
    • Phosphorus
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier method contraception during study and for up to 3 months following completion of study treatment
  • No impaired cardiac function, including any of the following:

    • LVEF < 45% by MUGA scan or echocardiogram
    • Uncontrolled congestive heart failure
    • Uncontrolled hypertension
    • Uncontrolled angina pectoris
    • Myocardial infarction within the past 12 months
  • No significant electric heart abnormalities, including any of the following:

    • History or active ventricular or atrial tachyarrhythmias
    • Congenital long QT syndrome and/or QTc > 450 msec on screening ECG
  • No history of acute (within one year) or chronic pancreatitis
  • No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • No acute or chronic liver or renal disease considered unrelated to leukemia
  • No known diagnosis of HIV infection
  • No 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
  • No other primary malignancy that is currently clinically significant or requires active intervention


  • More than 2 weeks since prior major surgery and recovered
  • More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days
  • More than 4 weeks since prior investigational drug
  • No prior hematopoietic stem cell transplantation
  • No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol, phenprocoumon)
  • No concurrent medications that would prolong the QT interval
  • No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy
  • Prior treatment with hydroxyurea or anagrelide allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00769327

Centro Oncologico Basilicata
Rionero in Vulture, Potenza, Italy
Ospedale Civile Alessandria
Alessandria, Italy, I-15100
Dipartimento Area Medica P.O.
Ascoli Piceno, Italy, 63100
S.G. Moscati Hospital
Avellino, Italy, 83100
Unità Operativa Ematologia 1 - Università degli Studi di Bari
Bari, Italy, 70010
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
Bologna, Italy
ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO
Cagliari, Italy
Unità di Oncoematologia Azienda Ospedaliera Garibaldi
Catania, Italy
Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
Catanzaro, Italy
Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
Ferrara, Italy, 44100
Azienda Ospedaliera di Firenze
Firenze, Italy, 50011
Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
Foggia, Italy
Clinica Ematologica - DiMI - Università degli Studi di Genova
Genova, Italy
Clinica Ematologica - Università degli Studi
Genova, Italy
A.O. Universitaria Policlinico Martina di Messina
Messina, Italy
Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte"
Messina, Italy
Sez. di medicina Interna Oncologia ed Ematologia
Modena, Italy
Universtià degli Studi di Napoli "Federico II" - Facoltà di medicina e chirurgia
Napoli, Italy
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
Novara, Italy
Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga
Orbassano, Italy
Ospedali Riuniti "Villa Sofia-Cervello"
Palermo, Italy
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy, 65100
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
Piacenza, Italy
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
Unità operativa complessa di Ematologia
Reggio Emilia, Italy
A.O Umberto I
Roma, Italy
Complesso Ospedaliero S. Giovanni Addolorata
Roma, Italy
Ospedale S.Eugenio
Roma, Italy
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
S. G. Rotondo, Italy
U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
Siena, Italy, 53100
Azienda ospedaliera S. Maria di Terni
Terni, Italy
SCDO Ematologia 2 AOU S.Giovanni Battista
Torino, Italy
Policlinico Universitario Udine
Udine, Italy, 33100
Policlinico G. B. Rossi - Borgo Roma
Verona, Italy, 37134
Ospedale San Bortolo
Vicenza, Italy, 36100
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Principal Investigator: Michele Baccarani, MD Gruppo Italiano Malattie EMatologiche dell'Adulto

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT00769327     History of Changes
Other Study ID Numbers: CML0408
First Posted: October 9, 2008    Key Record Dates
Last Update Posted: January 28, 2015
Last Verified: January 2015

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
chronic myelogenous leukemia, BCR-ABL1 positive
chronic phase chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action