Description:
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.
Title
- Brief Title: Activity and Risk Profile of Ponatinib in Chronic Phase Patients With Chronic Myeloid Leukemia Resistant to Imatinib
- 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
Clinical Trial IDs
- ORG STUDY ID:
CML1315
- SECONDARY ID:
2015-001102-34
- NCT ID:
NCT02398825
Conditions
- Chronic Myeloid Leukemia
- Chronic Phase
- Adults
Interventions
Drug | Synonyms | Arms |
---|
Ponatinib | | Ponatinib |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Ponatinib | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
1. Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL1+ CML
2. Age ≥ 18 years
3. Chronic phase CML
4. Prior treatment with imatinib, any dose
5. Resistance to imatinib, as defined by any one of the ELN 2013 failure criteria, as
follows:
- no complete hematologic response (CHR) at 3 months
- 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
6. For females of childbearing potential, a negative pregnancy test must be documented
prior to enrolment
7. An effective form of contraception with their sexual partners from enrolment through 4
months after the end of treatment
8. Signed written informed consent according to ICH/EU/GCP and national local laws prior
to any study procedures
9. Willingness and ability to comply with scheduled visits and study procedures.
Exclusion Criteria:
1. Accelerated or blastic phase CML
2. Patients previously treated with nilotinib or dasatinib
3. Patients with the T315I mutation
4. History of acute pancreatitis within 1 year of study or history of chronic
pancreatitis or of alcohol abuse
5. 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)
6. Compelled to take medications that are known to be associated with Torsades de Pointes
and/or with significant QTc prolongation
7. Pregnant or breastfeeding
8. Any condition or illness that, in the opinion of the Investigator, would compromise
patient safety or interfere with the evaluation of the drug
9. Lack of informed consent
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients with major cytogenetic response |
Time Frame: | After 52 weeks of ponatinib treatment start |
Safety Issue: | |
Description: | 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:
Major Cytogenetic Response if Ph pos metaphases < 35%
Complete (CCyR) if Ph pos metaphases 0 or FISH BCR-ABL1 nuclei minor or equal to 1%
Partial (PCyR) if Ph pos metaphases 1-34%
Minor (mCyR) if Ph pos metaphases 35-65%
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. |
Secondary Outcome Measures
Measure: | Number of Cardiovascular Adverse Events (AEs) |
Time Frame: | After three years from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of blood hypertension AEs |
Time Frame: | After three years from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of pancreatitis AEs |
Time Frame: | After three years from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients achieving Complete Cytogenetic Response (CCyR) |
Time Frame: | After 52 weeks of ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients achieving major molecular response |
Time Frame: | After 52 weeks of ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients with failure-free survival |
Time Frame: | At 36 months from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients with progression-free survival |
Time Frame: | At 36 months from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients in overal survival |
Time Frame: | At 36 months from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Number of patients in event-free survival |
Time Frame: | At 36 months from ponatinib treatment start |
Safety Issue: | |
Description: | |
Measure: | Quality of Life patterns over time with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires |
Time Frame: | At baseline and at at weeks 4, 12, 24, 36 and 52 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Gruppo Italiano Malattie EMatologiche dell'Adulto |
Trial Keywords
- Chronic myeloid leukemia
- Chronic phase
- Adults
- Ponatinib
- Imatinib resistant
Last Updated
August 19, 2021