This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI
Name: ABL001
Description: Adverse events (AEs) and serious adverse events (SAEs) will be summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) will be reported as adverse events and or serious adverse events as determined by the investigator.
Measure: Number of Adverse Events and Serious Adverse Events for cohorts A and B up to 24 weeks Time: Baseline to up to 24 WeeksDescription: Adverse events (AEs) and serious adverse events (SAEs) will be summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) will be reported as adverse events and or serious adverse events as determined by the investigator.
Measure: Number of Adverse Events and Serious Adverse Events for cohorts A, B and C up to 24 weeks Time: Baseline up to 48 and 72 weeksDescription: A complete hematologic response (CHR) is defined as all of the following present for ≥ 4 weeks: white blood count (WBC) <10 x 109/L, platelet count <450 x 109/L, basophils <5%, no blasts and promyelocytes in peripheral blood, myelocytes + metamyelocytes < 5% in peripheral blood, no evidence of extramedullary disease, including spleen and liver
Measure: Percentage of patients achieving complete hematologic response (CHR) for Cohorts A, B and C Time: Baseline to 12, 24, 48, 72 weeksDescription: The rate of molecular response (MR2) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 2 log reduction of BCR-ABL (transcript from standardized baseline or ≤ 1% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome. Rate for MMR is defined as ≥ 3 log reduction, MR4 is defined as ≥ 4 log reduction and MR4.5 is defined as ≥ 4.5 log reduction.
Measure: Percentage of patients achieving molecular response (MR2), major molecular response (MMR) and molecular response of MR4 and MR4.5 for cohorts A, B and C Time: Baseline up to 12, 24, 48, 72 weeksDescription: Time to achieving a response level is defined as the time from the date of the first dose of study medication to the first documented achievement of a each defined response level. Time to achieve a specific response level will be analyzed using the Kaplan-Meier Product-Limit method. Patients who are known to be without achieving that response level will be censored at the last adequate assessment.
Measure: Time to achieve CHR, MR2, MMR, MR4, MR4.5 for cohorts A, B and C Time: Baseline up to 72 weeksDescription: Duration of Response (DOR) is the time from the date of the first documented a molecular response level to the date of first documented loss of the response level or death due to any cause, whichever occurs first. DOR for each response level will be analyzed using the Kaplan-Meier Product-Limit method. Participants continuing without that event will be censored at the date of their last adequate response assessment.
Measure: Duration of CHR, MR2, MMR, MR4 and MR4.5 for cohorts A, B and C Time: Baseline up 72 weeksDescription: Progression Free Survival (PFS) is defined as time from the first dose of study medication to disease progression to accelerated phase/blast crisis (AP/BC) or death due to any cause, whichever occurs first. PFS will be analyzed using the Kaplan-Meier Product-Limit method
Measure: Progression Free Survival (PFS) for cohorts A, B and C Time: Baseline up to 72 weeksDescription: Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause during study. If a patient is not known to have died, then OS will be censored at the latest date the patient was known to be alive. OS will be analyzed using the Kaplan-Meier Product-Limit method
Measure: Overall Survival Overall Survival (OS) for cohorts A, B and C Time: Baseline up to 72 weeksAllocation: Randomized
Single Group Assignment
There is one SNP
An Open Label, Multi-center Phase IIIb Study of Asciminib (ABL001) Monotherapy in Previously Treated Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation. --- T315I ---
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI Number of Adverse Events and Serious Adverse Events for cohorts A and B up to 24 weeks. --- T315I ---
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI Number of Adverse Events and Serious Adverse Events for cohorts A and B up to 24 weeks. --- T315I --- --- T315I ---
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI Number of Adverse Events and Serious Adverse Events for cohorts A and B up to 24 weeks. --- T315I --- --- T315I --- --- T315I ---
imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of absence of T315I mutation • 1 prior ATP site TKI (i.e. --- T315I ---
imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of presence of T315I mutation 6. --- T315I ---
One hundred and fifteen (115) patients with chronic myeloid leukemia in chronic phase (CML-CP) without T315I mutation who have had at least 2 prior Tyrosine Kinase Inhibitors (TKIs) and CML-CP with the T315I mutation with at least 1 prior TKI will be considered for the current study Informed consent will be obtained before any procedures are performed for the study including eligibility assessments. --- T315I ---
One hundred and fifteen (115) patients with chronic myeloid leukemia in chronic phase (CML-CP) without T315I mutation who have had at least 2 prior Tyrosine Kinase Inhibitors (TKIs) and CML-CP with the T315I mutation with at least 1 prior TKI will be considered for the current study Informed consent will be obtained before any procedures are performed for the study including eligibility assessments. --- T315I --- --- T315I ---
Patients with CML-CP without T315I mutation will be randomly assigned to either cohort A or B. Patients with the T315I mutation will be enrolled in cohort C. --- T315I ---
Patients with CML-CP without T315I mutation will be randomly assigned to either cohort A or B. Patients with the T315I mutation will be enrolled in cohort C. --- T315I --- --- T315I ---