Cardiovascular Assessment of Ponatinib as Third Line Treatment in Chronic Phase Chronic Myeloid Leukemia
CarPAs
2 other identifiers
interventional
50
1 country
13
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2021
Typical duration for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 12, 2021
CompletedFirst Posted
Study publicly available on registry
January 14, 2021
CompletedStudy Start
First participant enrolled
February 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2025
CompletedFebruary 3, 2021
January 1, 2021
3.7 years
January 12, 2021
January 31, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (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
1 year
Study Arms (1)
Total Patients
EXPERIMENTALIntolerant 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.
Interventions
Ponatinib 15 mg tablet, taken orally once daily
Ponatinib 30 mg tablet, taken orally once daily
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- +3 more criteria
You may not qualify if:
- 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.
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Presidio Ospedaliero "Oncologico Businco" - Cagliari (CA)
Cagliari, 09121, Italy
AOU "Policlinico Vittorio Emanuele" - Catania (CT)
Catania, 95124, Italy
Ospedale San Gerardo - Monza (MB)
Milan, 20090, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Milano (MI)
Milan, 20122, Italy
Azienda Ospedaliera Universitaria "Federico II" - Napoli (NA)
Napoli, 80131, Italy
Fondazione IRCCS Policlinico San Matteo - Pavia (PV)
Pavia, 27100, Italy
Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" - Reggio Calabria (RC)
Reggio Calabria, 89133, Italy
AUSL Reggio Emilia (RE)
Reggio Emilia, 42122, Italy
ASL Roma 2 "Ospedale S. Eugenio" - Roma (RM)
Roma, 00144, Italy
AOU Policlinico Umberto I "Università La Sapienza" - Roma (RM)
Roma, 00161, Italy
Azienda Ospedaliero-Universitaria Senese - Siena (SI)
Siena, 53100, Italy
AOU Città della Salute e della Scienza - Torino (TO)
Torino, 10126, Italy
AOU Integrata Verona "Ospedale Borgo Roma" - Verona (VN)
Verona, 37134, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carlo Gambacorti
Ospedale San Gerardo - Monza (MI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 12, 2021
First Posted
January 14, 2021
Study Start
February 1, 2021
Primary Completion
October 31, 2024
Study Completion
April 1, 2025
Last Updated
February 3, 2021
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will not share