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

January 31, 2021 updated by: Associazione Italiana Pazienti Leucemia Mieloide Cronica

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Cagliari, Italy, 09121
        • Presidio Ospedaliero "Oncologico Businco" - Cagliari (CA)
        • Contact:
        • Principal Investigator:
          • Giovanni Caocci
      • Catania, Italy, 95124
        • AOU "Policlinico Vittorio Emanuele" - Catania (CT)
        • Contact:
        • Principal Investigator:
          • Fabio Stagno
      • Milano, Italy, 20090
      • Milano, Italy, 20122
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria "Federico II" - Napoli (NA)
        • Contact:
        • Principal Investigator:
          • Luigia Luciano
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo - Pavia (PV)
        • Contact:
        • Principal Investigator:
          • Chiara Elena
      • Reggio Calabria, Italy, 89133
        • Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" - Reggio Calabria (RC)
        • Contact:
        • Principal Investigator:
          • Bruno Martino
      • Reggio Emilia, Italy, 42122
      • Roma, Italy, 00144
        • ASL Roma 2 "Ospedale S. Eugenio" - Roma (RM)
        • Contact:
        • Principal Investigator:
          • Elisabetta Abruzzese
      • Roma, Italy, 00161
        • AOU Policlinico Umberto I "Università La Sapienza" - Roma (RM)
        • Contact:
        • Principal Investigator:
          • Roberto Latagliata
      • Siena, Italy, 53100
        • Azienda Ospedaliero-Universitaria Senese - Siena (SI)
        • Contact:
      • Torino, Italy, 10126
        • AOU Città della Salute e della Scienza - Torino (TO)
        • Contact:
        • Principal Investigator:
          • Patrizia Pregno
      • Verona, Italy, 37134

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures.
  2. CML diagnosis, Chronic Phase (CP), treated with imatinib and bosutinib. Previous treatment with dasatinib or nilotinib will not be allowed.
  3. Resistant or intolerant to imatinib and/or bosutinib.
  4. Able to take oral therapy.
  5. Female or male, 18 years of age or older.
  6. ECOG performance status 0-2.
  7. Minimum life expectancy of 3 months or more.

  8. 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
  9. Normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
  10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  11. 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.
  12. For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.

Exclusion Criteria:

  1. Current treatment on another therapeutic clinical trial.
  2. 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.
  3. 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.
  4. Take medications that are known to be associated with Torsades de Pointes.
  5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
  6. Have previously been treated with ponatinib.
  7. 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.

  8. Have significant or active cardiovascular disease, specifically including, but not restricted to:

    1. Myocardial infarction within 3 months prior to first dose of ponatinib,
    2. History of clinically significant atrial arrhythmia or any ventricular arrhythmia,
    3. Unstable angina within 3 months prior to first dose of ponatinib,
    4. Congestive heart failure within 3 months prior to first dose of ponatinib.
  9. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
  10. Have a history of pancreatitis or alcohol abuse.
  11. Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL).
  12. Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.
  13. 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).
  14. Pregnancy or breastfeeding.
  15. 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.
  16. 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.
  17. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Total Patients
Intolerant 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.
Drug: Ponatinib 15mg QD
Ponatinib 15 mg tablet, taken orally once daily
Other Names:
  • AP24534
  • ICLUSIG
Drug: Ponatinib 30mg QD
Ponatinib 30 mg tablet, taken orally once daily
Other Names:
  • AP24534
  • ICLUSIG

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Associazione Italiana Pazienti Leucemia Mieloide Cronica

Investigators

  • Principal Investigator: Carlo Gambacorti, Ospedale San Gerardo - Monza (MI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

February 1, 2021

Primary Completion (ANTICIPATED)

October 31, 2024

Study Completion (ANTICIPATED)

April 1, 2025

Study Registration Dates

First Submitted

January 12, 2021

First Submitted That Met QC Criteria

January 12, 2021

First Posted (ACTUAL)

January 14, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 3, 2021

Last Update Submitted That Met QC Criteria

January 31, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AssociazioneIPLMC
  • 2018-001334-18 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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