DASATINIB for Chronic myeloid leukemia

Inclusion criteria

• {"criterion_text":"- 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\n- Age >= 18 years\n- Signed informed consent to study participation\n- Typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale\n- Treatment of TKI either in the first line or in the second or other lines for intolerance only\n- TKI treatment> 4 years\n- Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)\n- Deep molecular response >= MR4.0 lasting > 2 years\n- 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

• {"criterion_text":"- 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\n- Pregnancy and breastfeeding\n- Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria\n- Non-quantifiable type of BCR-ABL1 transcript on an international scale\n- Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013\n- Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013\n- Previous allogeneic hematopoietic stem cell transplantation\n- Previous participation in a TKI withdrawal study with a real withdrawal history\n- 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\n- Life expectancy of less than 36 months due to severe concurrent disease\n- Severe concurrent disease that could limit adherence to study protocol or study completion"}

Primary endpoints

• {"endpoint_text":"- Proportion of patients in major molecular response (MMR) ie BCR-ABL1 (oncogenic BCR-ABL gene fusion transcript levels <= 0.1%) and Molecular Recurrence-Free Survival (MRFS, ie time from study entry to MMR loss, ie BCR-ABL1 transcript levels > 0.1% in 2 consecutive samples, or death from any cause) at month 6 after study entry","definition_or_measurement_approach":"MMR defined as BCR-ABL1 transcript levels <= 0.1%; MRFS defined as time from study entry to loss of MMR (BCR-ABL1 > 0.1% in two consecutive samples) or death. Measurement by quantitative BCR-ABL1 on the international scale at Month 6."}
• {"endpoint_text":"- Proportion of patients in major molecular response (MMR) and MRFS at month 12 after study entry","definition_or_measurement_approach":"MMR defined as BCR-ABL1 <= 0.1%; MRFS measured as time to loss of MMR or death; assessed at Month 12 by quantitative BCR-ABL1."}
• {"endpoint_text":"- Proportion of patients in MMR without treatment (TFR) and treatment-free survival (TFS, ie the time from withdrawal of TKI (tyrosin kinase inhibitors) to loss of MMR, reinitiation of TKI therapy from any cause, progression, or death from any cause) at month 18, 24 and 36 after study entry, ie, 6, 12 and 24 months after treatment discontinuation","definition_or_measurement_approach":"TFR = proportion in MMR without ongoing treatment; TFS defined as time from TKI withdrawal to loss of MMR, reinitiation of TKI, progression, or death. Assessed by serial quantitative BCR-ABL1 measurements at specified timepoints (months 18, 24, 36)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 will recover after TKI re-introduction","definition_or_measurement_approach":"Proportion losing MMR during dose de-escalation and proportion regaining MMR/MR4.0 after re-introduction of TKI; measured by BCR-ABL1 levels and MR4.0 thresholds."}
• {"endpoint_text":"- Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction","definition_or_measurement_approach":"Proportion losing MMR after discontinuation and proportion regaining MMR/MR4.0 after restarting TKI; assessed by serial BCR-ABL1 measurements."}
• {"endpoint_text":"- Time to re-establish MMR and MR4.0 after TKI restart","definition_or_measurement_approach":"Time (duration) from TKI re-initiation to achievement of MMR and MR4.0 as measured by quantitative BCR-ABL1."}
• {"endpoint_text":"- Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal","definition_or_measurement_approach":"Assessment of adverse event frequency/severity and temporal dynamics during two-step dose reduction; AE collection per study schedule."}
• {"endpoint_text":"- Assessment of TKI withdrawal syndrome (proportion of patients with development of withdrawal syndrome, severity of symptoms, time to first complaint, duration of complaints, therapeutic intervention)","definition_or_measurement_approach":"Measure proportion developing withdrawal syndrome, record severity, time to onset, duration, and any therapeutic interventions; based on clinical assessment and patient-reported complaints."}
• {"endpoint_text":"- Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome","definition_or_measurement_approach":"Correlation analysis between prior TKI adverse effects and occurrence/severity of withdrawal syndrome using collected AE and symptom data."}
• {"endpoint_text":"- Correlation of BCR-ABL1 kinetics (number of BCR-ABL1 transcripts in time) during TKI therapy with potential molecular relapse after TKI discontinuation","definition_or_measurement_approach":"Analysis of BCR-ABL1 transcript kinetics over time during therapy and association with molecular relapse after discontinuation; measured by serial quantitative BCR-ABL1."}
• {"endpoint_text":"- Correlation of the effect of TKI dose reduction and subsequent discontinuation with lipid metabolism and glycemia","definition_or_measurement_approach":"Assessment of changes in lipid profile and glycemia in relation to TKI dose reduction and discontinuation; measured by laboratory tests for lipids and glucose."}

Czechia

Earliest CTIS Part Ii Submission Date

21-05-2024

Latest Decision Or Authorization Date

06-11-2025

Processing Time Days

534

Number Of Sites

8

Number Of Participants

221

Primary sponsor

Full Name

Masarykova Univerzita

Organisation Type

Educational Institution

Country Of Registered Address

Czechia