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LeukemiaPhase 2CML0408NCT00769327

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

A Phase 2 study testing imatinib mesylate, nilotinib and cytogenetic analysis in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 37 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

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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Leukemia
What is being tested?
imatinib mesylate, nilotinib and cytogenetic analysis
How many people
129 participants
Where
37 sitesItaly
Study dates
9 Feb 2009to 10 Oct 2014
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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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

Trial locations and contacts

37 sites in 1 country.

37 sites in 1 country

Italy37 sites

  • Ospedale Civile Alessandria

    Alessandria, I-15100

  • Dipartimento Area Medica P.O.

    Ascoli Piceno, 63100

  • S.G. Moscati Hospital

    Avellino, 83100

  • Unità Operativa Ematologia 1 - Università degli Studi di Bari

    Bari, 70010

  • Ospedali Riuniti di Bergamo

    Bergamo, 24100

  • Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

    Bologna

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

    Cagliari

  • Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania

    Catania

  • Unità di Oncoematologia Azienda Ospedaliera Garibaldi

    Catania

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

    Catanzaro

  • Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

    Ferrara, 44100

  • Azienda Ospedaliera di Firenze

    Florence, 50011

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

    Foggia

  • Clinica Ematologica - DiMI - Università degli Studi di Genova

    Genova

  • Clinica Ematologica - Università degli Studi

    Genova

  • A.O. Universitaria Policlinico Martina di Messina

    Messina

  • Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte"

    Messina

  • Sez. di medicina Interna Oncologia ed Ematologia

    Modena

  • Universtià degli Studi di Napoli "Federico II" - Facoltà di medicina e chirurgia

    Naples

  • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

    Novara

  • Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga

    Orbassano

  • Ospedali Riuniti "Villa Sofia-Cervello"

    Palermo

  • U.O. Ematologia Clinica - Azienda USL di Pescara

    Pescara, 65100

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

    Piacenza

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

    Reggio Calabria

  • Unità operativa complessa di Ematologia

    Reggio Emilia

  • Centro Oncologico Basilicata

    Rionero in Vulture, Potenza

  • A.O Umberto I

    Roma

  • Complesso Ospedaliero S. Giovanni Addolorata

    Roma

  • Ospedale S.Eugenio

    Roma

  • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

  • U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

    Siena, 53100

  • Azienda ospedaliera S. Maria di Terni

    Terni

  • SCDO Ematologia 2 AOU S.Giovanni Battista

    Torino

  • Policlinico Universitario Udine

    Udine, 33100

  • Policlinico G. B. Rossi - Borgo Roma

    Verona, 37134

  • Ospedale San Bortolo

    Vicenza, 36100

Other trials in Italy

About this study

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.

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.

Read the detailed description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Conditions
Leukemia
Being tested
imatinib mesylate, nilotinib, cytogenetic analysis, fluorescence in situ hybridization, microarray analysis
Keywords
chronic myelogenous leukemia, BCR-ABL1 positive, chronic phase chronic myelogenous leukemia
Medical subject headings
Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase

What participants receive

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

  • imatinib mesylateDrug

  • nilotinibDrug

  • cytogenetic analysisGenetic

  • fluorescence in situ hybridizationGenetic

  • microarray analysisGenetic

  • mutation analysisGenetic

  • polymerase chain reactionGenetic

  • polymorphism analysisGenetic

  • laboratory biomarker analysisOther

What is being measured

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

  1. Complete cytogenetic response rate

    Measured: At 12 months from study entry

Secondary outcomes (7)

  1. Complete cytogenetic response

    Measured: At at 6 and 24 months from study entry

  2. Major and complete molecular response rate

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

  3. Development of BCR-ABL kinase domain mutations (number, timing, and type)

    Measured: At at 24 months during and for 3 years after study treatment

  4. Rate of failures and the time to failure

    Measured: At 12, 24, and 60 months from study entry

  5. Safety and tolerability

    Measured: At 24 months from study entry

  6. Frequency and type of adverse events (AE) and severe AE

    Measured: 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

    Measured: At 24 months from study entry

Timeline

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

  1. First posted9 Oct 2008 (estimated)
  2. Study start9 Feb 2009
  3. Primary completionOct 2014
  4. Study completion10 Oct 2014

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
129 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00769327
Sponsor's protocol ID
CML0408
Other IDs
GIMEMA-CML0408, EUDRACT-2008-004384-19, EU-20881
Acronym
CML0408
Status last verified
Jan 2022
First submitted
8 Oct 2008
Last updated
4 Jan 2022
Results posted
No
Data monitoring committee
No

Publications

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing imatinib mesylate, nilotinib and cytogenetic analysis in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 37 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?

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 4 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 37 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 rate (time frame: At 12 months from study entry). 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 NCT00769327, 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 4 Jan 2022.

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