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Chronic Myeloid LeukemiaPhase 2NCT02398825

Activity and Risk Profile of Ponatinib in Chronic Phase Patients With Chronic Myeloid Leukemia Resistant to Imatinib

A Phase 2 study testing Ponatinib in people with Chronic Myeloid Leukemia and Chronic Phase, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 37 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study aims at evaluating the efficacy of treatment with ponatinib in patients with chronic myeloid leukemia who are in a chronic phase and who previously received treatment with imatinib but resulted to be resistant to it. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia, Chronic Phase, Adults
What is being tested?
Ponatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
37 sitesItaly
Study dates
23 Jun 2016to 27 Dec 2022
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

  • Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL1+ CML
  • Age ≥ 18 years
  • Chronic phase CML
  • Prior treatment with imatinib, any dose
  • Resistance to imatinib, as defined by any one of the ELN 2013 failure criteria, as follows:
  • no complete hematologic response (CHR) at 3 months
Show all 19Show fewer
  • no cytogenetic response (CyR) (Ph+ > 95%) at 3 months
  • Less than partial CyR (PCyR, Ph+ > 35%) at 6 months
  • BCR-ABL1 > 10% at 6 months
  • Non complete CyR (CCyR) (Ph+ > 0%) at 12 months
  • BCR-ABL1 > 1% at 12 months
  • Loss of CHR, at any time
  • Loss of CCyR, at any time
  • Confirmed loss of major molecular response (MMR) (BCR-ABL1 bigger or equal to 0.1% in two consecutive tests, of which one bigger or equal to 1%), at any time
  • Any new BCR-ABL1 mutation, at any time
  • For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment
  • An effective form of contraception with their sexual partners from enrolment through 4 months after the end of treatment
  • Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedures
  • Willingness and ability to comply with scheduled visits and study procedures.

Who cannot join

  • Accelerated or blastic phase CML
  • Patients previously treated with nilotinib or dasatinib
  • Patients with the T315I mutation
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis or of alcohol abuse
  • Patients with history of acute myocardial infarction (AMI), unstable angina or coronary heart disease (CHD), congestive heart failure, cerebrovascular events (CVE) (stroke or transitory ischemic attack), or peripheral artery occlusive disease (PAOD)
  • Compelled to take medications that are known to be associated with Torsades de Pointes and/or with significant QTc prolongation
Show all 9Show fewer
  • Pregnant or breastfeeding
  • Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug
  • Lack of informed consent

Trial locations and contacts

37 sites in 1 country.

37 sites in 1 country

Italy37 sites

  • Aos Ss. Antonio E Biagio E C. Arrigo - Soc Ematologia

    Alessandria

  • Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi

    Ancona

  • Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

    Bologna, 40138

  • Asst Degli Spedali Civili Di Brescia - Uo Ematologia

    Brescia

  • Ao Brotzu, Presidio Ospedaliero A. Businco - Sc Ematologia E Ctmo

    Cagliari

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

    Catania

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

    Catania

  • Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia

    Catanzaro

  • Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione

    Cona

  • Aso S. Croce E Carle - Cuneo - Sc Ematologia

    Cuneo

  • Irccs Aou San Martino - Genova - Uo Clinica Ematologica

    Genova

  • Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

    Lecce

  • .R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica

    Meldola

  • Aou Policlinico "G. Martino" - Messina - Uoc Ematologia

    Messina

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano

    Milan

  • Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

    Milan

  • Milano Unità Trapianto di Midollo Ist. Nazionale Tumori

    Milan

  • Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo

    Naples

  • Aou Federico Ii - Napoli - Uoc Ematologia

    Naples

  • Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia

    Orbassano

  • Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo

    Palermo

  • Aou Policlinico P. Giaccone - Palermo - Uo Ematologia

    Palermo

  • Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia

    Pavia

  • Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica

    Pescara

  • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto

    Piacenza

  • Aou Pisana - Uo Ematologia Universitaria

    Pisa

  • Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia

    Ravenna

  • Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia

    Rimini

  • Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali

    Roma

  • Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia

    Roma

  • Roma Uoc Pronto Soccorso E Accettazione Ematologica - Dipartimento Biotecnologie Cellulari Ed Ematologia - Università Degli Studi Di Roma "Sapienza"

    Roma

  • Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia

    San Giovanni Rotondo

  • Aou Senese - Uoc Ematologia E Trapianti

    Siena

  • Ao S. Maria - Terni - Sc Onco Ematologia

    Terni

  • Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana

    Treviso

  • Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia

    Verona

  • Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia

    Vicenza

Other trials in Italy

About this study

Official title: Optimizing Ponatinib USe (OPUS). A GIMEMA Phase 2 Study of the Activity and Risk Profile of Ponatinib, 30 mg Once Daily, in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients Resistant to Imatinib

This study aims at evaluating the efficacy of treatment with ponatinib in patients with chronic myeloid leukemia who are in a chronic phase and who previously received treatment with imatinib but resulted to be resistant to it.

Read the detailed description

Phase 2, single-arm, multicentre, open label. No interim analysis is planned, but a monitoring committee will evaluate the data every 6 months. Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level smaller or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol. Treatment time will be 52 weeks, during which study drug will be provided free-of-charge by ARIAD Pharmaceuticals, upon approval of the protocol. Treatment is discontinued at any time in case of failure or treatment-related SAEs. After one year of treatment, upon request of the local investigator and upon confirmation of the Treatment Advisory Committee (TAC, see section 23), ARIAD Pharmaceutics, Inc. will continue to provide ponatinib for the study patients who will benefit from treatment continuation, for at least 2 years, until the drug will be approved with that indication.

Being tested
Ponatinib
Keywords
Chronic myeloid leukemia, Chronic phase, Adults, Ponatinib, Imatinib resistant
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.

  • PonatinibDrug

    Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level minor or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol.

Study groups in NCT02398825
Study groupRoleWhat they receive
PonatinibExperimentalNot described
Receives: Drug: Ponatinib

What is being measured

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

  1. Number of patients with major cytogenetic response

    Cytogenetic response (CyR) is defined based on the percentage of Ph pos metaphases, as evaluated by chromosome banding analysis (CBA) of at least 20 marrow cell metaphases:

    1. Major Cytogenetic Response if Ph pos metaphases < 35%
    2. Complete (CCyR) if Ph pos metaphases 0 or FISH BCR-ABL1 nuclei minor or equal to 1%
    3. Partial (PCyR) if Ph pos metaphases 1-34%
    4. Minor (mCyR) if Ph pos metaphases 35-65%
    5. Minimal or none (min/none CyR) if Ph pos metaphases > 65% If marrow cell metaphases cannot be obtained or analysed, interphase fluorescence-in-situ-hybridization (FISH) can be used, but only to distinguish a CCyR (minor or equal to 1% positive nuclei out of at least 200 nuclei) from a non CCyR. FISH data cannot be used to classify a response as minimal, minor, or partial.

    Measured: After 52 weeks of ponatinib treatment start

Secondary outcomes (10)

  1. Number of Cardiovascular Adverse Events (AEs)

    Measured: After three years from ponatinib treatment start

  2. Number of blood hypertension AEs

    Measured: After three years from ponatinib treatment start

  3. Number of pancreatitis AEs

    Measured: After three years from ponatinib treatment start

  4. Number of patients achieving Complete Cytogenetic Response (CCyR)

    Measured: After 52 weeks of ponatinib treatment start

  5. Number of patients achieving major molecular response

    Measured: After 52 weeks of ponatinib treatment start

  6. Number of patients with failure-free survival

    Measured: At 36 months from ponatinib treatment start

  7. Number of patients with progression-free survival

    Measured: At 36 months from ponatinib treatment start

  8. Number of patients in overal survival

    Measured: At 36 months from ponatinib treatment start

  9. Number of patients in event-free survival

    Measured: At 36 months from ponatinib treatment start

  10. Quality of Life patterns over time with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires

    Measured: At baseline and at at weeks 4, 12, 24, 36 and 52

Timeline

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

  1. First posted26 Mar 2015 (estimated)
  2. Study start23 Jun 2016
  3. Primary completion13 Nov 2020
  4. Study completion27 Dec 2022

Why it stopped: low enrollment rate

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
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02398825
Sponsor's protocol ID
CML1315
Other IDs
2015-001102-34, 2015
Status last verified
Jan 2025
First submitted
15 Mar 2015
Last updated
17 Jan 2025
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib in people with Chronic Myeloid Leukemia and Chronic Phase, 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?

The sponsor lists 19 inclusion and 9 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: stopped early, as of the sponsor's last update on 17 Jan 2025. 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 was stopped early (reason given: low enrollment rate). Results are not available in the source record.

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?

Number of patients with major cytogenetic response (time frame: After 52 weeks of ponatinib treatment start). 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 NCT02398825.

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 17 Jan 2025.

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