ABL001 for the Treatment of Chronic Myeloid Leukemia in Patients Who Are on Therapy With Tyrosine Kinase Inhibitor
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|ClinicalTrials.gov Identifier: NCT04216563|
Recruitment Status : Not yet recruiting
First Posted : January 2, 2020
Last Update Posted : April 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia||Drug: Asciminib||Phase 2|
I. To determine the clinical activity of the combination of asciminib (ABL001) and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) but detectable BCR-ABL1 transcript.
I. To determine the effect of the combination of ABL001 and TKI on the rate of mismatch repair (MR)4, MR4.5, and sustained MR4.5.
II. To investigate treatment-free remission after at least 2 years of sustained deep molecular remission.
III. To determine the safety of the combination of asciminib and tyrosine kinase inhibitors.
IV. To determine the event-free survival (EFS), survival free from transformation to accelerated and blast phase (TFS), and overall survival (OS).
I. To determine the rate of minimal residual disease (MRD) clearance using droplet digital polymerase chain reaction (ddPCR) detecting the BCR-ABL1 fusion transcript.
II. To determine the effect of therapy on quiescent leukemic Philadelphia chromosome positive (Ph+) stem cells (CFSEmax/CD34+).
III. To determine the effect of this combination on mutations in ABL1 and mutations in clonal hematopoiesis of indeterminate potential (CHIP)-associated genes using molecular barcode sequencing.
IV. To determine the effect of therapy on bone marrow progenitors in clonogenic assays.
V. To describe immune effects of the combination of TKI and ABL001. VI. To describe patient reported outcomes (PRO) using the MD Anderson Symptom Inventory (MDASI)-CML instrument.
Patients receive asciminib orally (PO) twice daily (BID) for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator.
After completion of study treatment, patients are followed up every 4-8 weeks for 6 months and then every 3-6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Dual Targeting of BCR-ABL1 by Adding the Allosteric Inhibitor ABL001 in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease (MRD) While on Therapy With Tyrosine Kinase Inhibitors|
|Estimated Study Start Date :||April 30, 2020|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
Experimental: Treatment (asciminib)
Patients receive asciminib PO BID for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator.
Other Name: ABL001
- Rate of molecular response [ Time Frame: At 12 months from the start of the study ]For each cohort, will estimate the response rate and 95% confidence interval.
- Event free survival [ Time Frame: Up to 6 years ]The Kaplan-Meier method will be used.
- Overall survival [ Time Frame: Up to 6 years ]The Kaplan-Meier method will be used.
- Treatment-free remission [ Time Frame: Up to 6 years ]Frequency, percentage and 95% confidence interval will be tabulated.
- Mismatch repair status [ Time Frame: Up to 6 years ]Frequency, percentage and 95% confidence interval will be tabulated.
- Interference score [ Time Frame: Up to 6 years ]Descriptive statistics will be provided.
- Rate of minimal residual disease (MRD) clearance [ Time Frame: Up to 6 years ]Descriptive statistics will be provided.
- MD Anderson Symptom Inventory (MDASI)-Chronic Myeloid Leukemia (CML) score [ Time Frame: Up to 6 years ]Descriptive statistics will be provided.
- Incidence of adverse events [ Time Frame: Up to 6 years ]Treatment-related unacceptable toxicity will be defined as grade 3 or 4 toxicity that prevents patients from continuing combination therapy despite optimal management.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04216563
|Contact: Ghayas C. Issafirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Contact: Ghayas C. Issa 713-745-6798|
|Principal Investigator: Ghayas C. Issa|
|Principal Investigator:||Ghayas C Issa||M.D. Anderson Cancer Center|