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

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Treatments: Imatinib Mesylate; Ponatinib

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