Consolidation Treatment With Ponatinib 15 mg on Treatment Free-Remission Rate in Patients With Chronic Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

Summary

Ponatinib has shown to induce deeper molecular responses compared with imatinib. Therefore, ponatinib treatment could increase the proportion of patients who could discontinue treatment successfully. This strategy that includes treatment change to a more powerful treatment before treatment discontinuation has not been evaluated in any of the previous clinical trials, and will be explored in the current study.

In this framework, the purpose is to determine the rate of successful treatment-free remission (TFR) within the first 48 weeks following cessation of treatment in patients who achieved Molecular Response 4 (MR4) on imatinib and maintained MR4 on ponatinib after a switch from imatinib. Eligible patients have been previously treated with imatinib as unique tyrosine kinase inhibitor (at least 4 years) and have documented MR4 (at least 12 months) at the time of switch to ponatinib to study entry.

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

Details

• Lead Sponsor: Fundación Teófilo Hernando, Spain
• Treatments: Ponatinib

Criteria

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.

2. ECOG performance status of 0, 1, or 2.

3. Patient with diagnosis of BCR-ABL positive CML-CP.

4. Patient has received a minimum of 4 years of imatinib treatment, as unique TKI therapy.

5. Patient has achieved MR4 during at least 12 months with imatinib treatment, and determined by PCR lab assessment at screening.

6. Adequate end organ function.

7. Patients must have the following electrolyte values ≥ LLN limits or corrected to within normal limits with supplements prior to the first dose of study medication: Potassium, Magnesium, Total calcium (corrected for serum albumin).

8. Patients must have normal marrow function

9. Patients with preexisting, well-controlled, diabetes are not excluded.

10. Have normal QTcF interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.

11. Have a negative pregnancy test documented prior to enrollment

12. Be willing and able to comply with scheduled visits and study procedures.

13. Written informed consent obtained prior to any screening procedures.

Exclusion Criteria:

1. Prior AP, BC or autologous or allogenic transplant.

2. Patients with known atypical transcript.

3. CML treatment resistant mutation(s).

4. Are taking medications with a known risk of torsades de pointes (Appendix A)

5. Patient ever attempted to permanently discontinue imatinib or ponatinib treatment.

6. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks.

7. Have clinically significant, uncontrolled, or active cardiovascular disease.

8. Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg).

9. Have a history of alcohol abuse.

10. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis.

11. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.

12. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer.

13. Have a history of another malignancy; the exception is if patients have been disease-free for at least 5 years.

14. Have undergone surgery within 14 days prior to first dose of ponatinib.

15. Treatment with other investigational within 4 weeks of Day 1.

16. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers.

17. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers.

18. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval.

19. Have an ongoing or active infection.

20. Have a known history of human immunodeficiency virus infection.

21. Have hypersensitivity to the ponatinib active substance or to any of its inactive ingredients.

22. Pregnant or nursing (lactating) women.