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Chronic Myeloid Leukemia (CML)Phase 2CarPAsNCT04709731

Cardiovascular Assessment of Ponatinib as Third Line Treatment in Chronic Phase Chronic Myeloid Leukemia

A Phase 2 study testing Ponatinib 15mg QD and Ponatinib 30mg QD in people with Chronic Myeloid Leukemia (CML), run by Associazione Italiana Pazienti Leucemia Mieloide Cronica at 13 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will address the therapeutic activity and the safety/biological profile of Ponatinib when used as third line therapy of Chronic Myeloid Leukemia in Chronic Phase after the only two TKIs known for their cardiovascular safety, i.e. Imatinib and Bosutinib. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Chronic Myeloid Leukemia (CML)
What is being tested?
Ponatinib 15mg QD and Ponatinib 30mg QD
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
13 sitesItaly
Study dates
1 Feb 2021to 1 Apr 2025
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 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures.
  • CML diagnosis, Chronic Phase (CP), treated with imatinib and bosutinib. Previous treatment with dasatinib or nilotinib will not be allowed.
  • Resistant or intolerant to imatinib and/or bosutinib.
  • Able to take oral therapy.
  • Female or male, 18 years of age or older.
  • ECOG performance status 0-2.
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  • Minimum life expectancy of 3 months or more.
  • Adequate organ function as defined by the following criteria:
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  • Total serum bilirubin ≤ 1.5 x ULN (except patients with documented Gilbert's syndrome)
  • Creatinine ≤ 1.5 x ULN
  • Prothrombin time (PT) < 1.5 × ULN
  • Lipase ≤ 1.5 × ULN for institution
  • Amylase ≤ 1.5 × ULN for institution
  • Normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Female and male patients who are of childbearing potential must agree to use an effective form of contraception (2 forms of contraception) with their partners throughout participation in this study and for at least 90 days after the last dose of treatment.
  • For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.

Who cannot join

  • Current treatment on another therapeutic clinical trial.
  • Received TKI therapy within 7 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by NCI CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
  • Underwent autologous or allogeneic stem cell transplant < 60 days prior to receiving the first dose of ponatinib; any evidence of on-going graft versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy.
  • Take medications that are known to be associated with Torsades de Pointes.
  • Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
  • Have previously been treated with ponatinib.
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  • Have active central nervous system (CNS) disease as evidenced by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
  • Have significant or active cardiovascular disease, specifically including, but not restricted to:
  • Myocardial infarction within 3 months prior to first dose of ponatinib,
  • History of clinically significant atrial arrhythmia or any ventricular arrhythmia,
  • Unstable angina within 3 months prior to first dose of ponatinib,
  • Congestive heart failure within 3 months prior to first dose of ponatinib.
  • Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
  • Have a history of pancreatitis or alcohol abuse.
  • Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL).
  • Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.
  • Have been diagnosed with another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ, or controlled prostate cancer, which are allowed within 3 years).
  • Pregnancy or breastfeeding.
  • Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of ponatinib.
  • Have ongoing or active infection (including known history of human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]). Testing for these viruses is not required in the absence of history.
  • Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration.

Trial locations and contacts

13 sites in 1 country.

Michaela De Palo contact

0283427930

michaela.depalo@galseq.com, studiclinici@galseq.com

Nicoletta Re contact

0258103979

aip.info@libero.it, re.nicoletta@outlook.com

13 sites in 1 country

Italy13 sites

  • Presidio Ospedaliero "Oncologico Businco" - Cagliari (CA)

    Cagliari, 09121

    Giovanni Caocci, Prof., giovanni.caocci@unica.it

    Giovanni Caocci

  • AOU "Policlinico Vittorio Emanuele" - Catania (CT)

    Catania, 95124

    Fabio Stagno, Dr., fsematol@tiscali.it

    Fabio Stagno

  • Ospedale San Gerardo - Monza (MB)

    Milan, 20090

    Carlo Gambacorti, Prof., carlo.gambacorti@unimib.it

    Carlo Gambacorti Passerini

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Milano (MI)

    Milan, 20122

    Alessandra Iurlo, Dr.ssa, alessandra.iurlo@policlinico.mi.it

    Alessandra Iurlo

  • Azienda Ospedaliera Universitaria "Federico II" - Napoli (NA)

    Naples, 80131

    Luigia Luciano, Dr.ssa, lulucian@unina.it

    Luigia Luciano

  • Fondazione IRCCS Policlinico San Matteo - Pavia (PV)

    Pavia, 27100

    Chiara Elena, Dr.ssa, chiara.elena1@gmail.com

    Chiara Elena

  • Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" - Reggio Calabria (RC)

    Reggio Calabria, 89133

    Bruno Martino, Dr., ematologiarc@alice.it

    Bruno Martino

  • AUSL Reggio Emilia (RE)

    Reggio Emilia, 42122

    Isabella Capodanno, Dr.ssa, capodanno.isabella@ausl.re.it

    Isabella Capodanno

  • ASL Roma 2 "Ospedale S. Eugenio" - Roma (RM)

    Roma, 00144

    Elisabetta Abruzzese, Dr.ssa, elisabetta.abruzzese@uniroma2.it

    Elisabetta Abruzzese

  • AOU Policlinico Umberto I "Università La Sapienza" - Roma (RM)

    Roma, 00161

    Roberto Latagliata, Dr., latagliata@bce.uniroma1.it

    Roberto Latagliata

  • Azienda Ospedaliero-Universitaria Senese - Siena (SI)

    Siena, 53100

    Monica Bocchia, Prof.ssa, bocchia@unisi.it

    Monica Bocchia

  • AOU Città della Salute e della Scienza - Torino (TO)

    Torino, 10126

    Patrizia Pregno, Dr.ssa, ppregno@cittadellasalute.to.it

    Patrizia Pregno

  • AOU Integrata Verona "Ospedale Borgo Roma" - Verona (VN)

    Verona, 37134

    Massimiliano Bonifacio, Dr., massimiliano.bonifacio@univr.it

    Massimiliano Bonifacio

Other trials in Italy

About this study

Official title: Cardiovascular Assessment of Ponatinib as Third Line Treatment Option in Chronic Phase Chronic Myeloid Leukemia After Failure of Imatinib and Bosutinib (CarPAs)

This study will address the therapeutic activity and the safety/biological profile of Ponatinib when used as third line therapy of Chronic Myeloid Leukemia in Chronic Phase after the only two TKIs known for their cardiovascular safety, i.e. Imatinib and Bosutinib.

Read the detailed description

Phase 2, single-arm, multicentre, open label study which aims to investigate the therapeutic activity and the cardiovascular safety profile of Ponatinib when used as third line therapy of Chronic Myeloid Leukemia in Chronic Phase, after using the only two Tyrosine Kinase Inhibitors (TKIs) known for the safest cardiovascular profile, i.e. Imatinib and Bosutinib. Patients will be stratified according to the cause of discontinuation of the second TKI: intolerance or resistance. The safety of Ponatinib will be assessed by a combination of clinical tests such as ECG, Doppler ultrasound studies to assess arterial and venous vessels, blood pressure monitoring and lipid profiles, combined with inflammatory cytokine analysis which is a known predictor of subsequent cardiovascular adverse events.

Being tested
Ponatinib 15mg QD, Ponatinib 30mg QD
Keywords
Chronic Myeloid Leukemia, Chronic Phase, Ponatinib, BCR-ABL Positive (BCR-ABL+), Philadelphia Chromosome Positive (Ph+), Imatinib and/or Bosutinib Intolerance, Imatinib and/or Bosutinib Resistance
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.

  • Ponatinib 15mg QDDrug

    Also called ICLUSIG, AP24534

    Ponatinib 15 mg tablet, taken orally once daily

  • Ponatinib 30mg QDDrug

    Also called ICLUSIG, AP24534

    Ponatinib 30 mg tablet, taken orally once daily

Study groups in NCT04709731
Study groupRoleWhat they receive
Total PatientsExperimentalIntolerant Group Ponatinib 15 mg tablet, taken orally once daily (QD) Resistant Group Ponatinib 30 mg tablet, taken orally once daily (QD) The dose will be reduced to 15mg once daily (QD) as soon as a Complete Cytogenetic Response will be obtained. In those patients showing Major Molecular Response or better, the dose could be further reduced to 15MG every other day (EOD), due to the prolonged half-life of the drug.
Receives: Drug: Ponatinib 15mg QD; Drug: Ponatinib 30mg QD

What is being measured

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

  1. Exposure adjusted Rate of Arterial Occlusive Events and Serious Arterial Occlusive Events at 1 year after study treatment initiation of each patient

    Exposure adjusted Rate of Arterial Occlusive Events (AOE) and Serious AOE (SOE) at 1 year after study treatment initiation of each patient

    Measured: 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 posted14 Jan 2021
  2. Study start1 Feb 2021 (estimated)
  3. Primary completion31 Oct 2024 (estimated)
  4. Study completion1 Apr 2025 (estimated)

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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04709731
Sponsor's protocol ID
AssociazioneIPLMC
Other IDs
2018-001334-18, 2018
Acronym
CarPAs
Status last verified
Jan 2021
First submitted
12 Jan 2021
Last updated
3 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib 15mg QD and Ponatinib 30mg QD in people with Chronic Myeloid Leukemia (CML), run by Associazione Italiana Pazienti Leucemia Mieloide Cronica at 13 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 18 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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?

Results are not available in the source record.

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

Contact Michaela De Palo (0283427930, michaela.depalo@galseq.com, studiclinici@galseq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Exposure adjusted Rate of Arterial Occlusive Events and Serious Arterial Occlusive Events at 1 year after study treatment initiation of each patient (time frame: 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 NCT04709731.

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 3 Feb 2021.

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