Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Evaluation of the efficacy and safety of withdrawal of tyrosine kinase inhibitors after previous two-step dose reduction in patients with chronic myeloid leukemia in deep molecular remission

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

Details

• Lead Sponsor: Masaryk University
• Treatments: Dasatinib; Imatinib Mesylate

Criteria

Inclusion Criteria:

1. Patients with documented Ph1-positive and / or BCR-ABL1-positive CML in a documented first chronic phase, the criteria of which are as follows:

• <15% blasts in peripheral blood (PB) or bone marrow (BM)

• <30% blasts + promyelocytes in PB or BM

• <20% of basophils in PB

• >= 100 billion / l platelets

• Absence of extramedullary involvement except hepato- and / or splenomegaly

2. Age >= 18 years

3. Signed informed consent to study participation

4. Typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale

5. Treatment of TKI either in the first line or in the second or other lines for intolerance only

6. TKI treatment> 4 years

7. Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)

8. Deep molecular response >= MR4.0 lasting > 2 years

9. Participants in a fertile clinical trial must agree to use prescribed contraceptive methods from entry to study until one year after the last dose of study medication:

• Women - Proper use of a highly reliable contraceptive method, ie combined hormonal contraceptives (in oral, vaginal or transdermal dosage form), gestagen hormonal contraceptives associated with ovulation inhibition (in oral or injectable dosage form), non-hormonal IUDs (intrauterine device) or IUDs , ev. presence of bilateral tubular occlusion, partner vasectomy, or adherence to sexual abstinence

• Men - Observance of sexual abstinence or use of adequate contraceptive method (ie condom) in the case of sexual intercourse for the period from enrollment to 1 year after the last dose of the drug

Exclusion Criteria:

1. Patients with Ph1-positive and / or BCR-ABL1-positive CML in the second chronic phase, in the accelerated phase or blast crisis (AP/BC) at any time in the history of the disease

2. Non-quantifiable type of BCR-ABL1 transcript on an international scale

3. Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013

4. Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013

5. Previous allogeneic hematopoietic stem cell transplantation

6. Previous participation in a TKI withdrawal study with a real withdrawal history

7. Previous discontinuation of TKI outside the study for other reasons (eg intolerance or pregnancy) lasting more than 9 months and / or if a treatment response was lost during less than 12 months prior to screening

8. Life expectancy of less than 36 months due to severe concurrent disease

9. Severe concurrent disease that could limit adherence to study protocol or study completion

10. Pregnancy and breastfeeding

11. Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria