Combination of BTK Inhibitor Overcomes Drug-resistance in Refractory/Relapsed FLT3 Mutant AML

Nanfang Hospital, Southern Medical University

Status and phase: Unknown; Phase 3; Phase 2

Conditions: FLT3-ITD Mutation; Brutons Tyrosine Kinase; Acute Myeloid Leukemia

Treatments: Drug: Ibrutinib

Study type: Interventional

Funder types: Other

Identifiers

NCT03642236

BTKi in FLT3 mutant AML

Details and patient eligibility

About

Clinical efficacy of FLT3 inhibitors combining with chemotherapy is usually transient and followed by emergence of drug-resistance in FLT3-ITD mutant AML. BTK is reported to be a therapeutic target in this subtype leukemia. Our previous study showed inhibition of BTK onvercome drug-resistance to FLT3 inhibitors/chemotherapy in refractory/relapsed FLT3 mutant AML. In this prospective randomized controlled study, the efficacy and safety of combination of BTK inhibitor with chemotherapy with/without FLT3 inhibitor in refractory/relapsed FLT3 mutant AML are evaluated.

Full description

Clinical efficacy of FLT3 inhibitors combining with chemotherapy is usually transient and followed by emergence of drug-resistance in FLT3-ITD mutant acute myeloid leukemia (AML). How to overcome the resistance to FLT3 inhibitors or chemotherapy needs further study. Bruton's tyrosine kinase (BTK) is reported to be a therapeutic target in this subtype leukemia. Our previous study showed inhibition of BTK onvercome drug-resistance to FLT3 inhibitors/chemotherapy in refractory/relapsed FLT3 mutant AML. In this prospective randomized controlled study, we are going to inhibit BTK with BTK inhibitor ibrutinib in the patients with refractory/relapsed FLT3 mutant AML, and then test the enhancing effect and safety of combination of ibrutinib with chemotherapy with/without FLT3 inhibitor, to make sure inhibition of BTK overcomes drug-resistance in FLT3 mutation AML.

Enrollment: 122 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Refractoty/relapsed FLT3-ITD mutation AML Age 14-60

Exclusion criteria

Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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122 participants in 2 patient groups

BTK treatment

Experimental group

Description:

Ibrutinib 420mg day -3 to d14; Decitabine 20mg/m2 d1-5; Aclacinomycin 10mg/m2 d1-5; Cytarabine 15mg/m2 q12h d1-14; G-CSF 200ug/m2 -12h to d14; Sorafenib 0.4g bid continously at the condition of being naive to sorafenib.

Treatment:

Drug: Ibrutinib

BTK-free treatment

Active Comparator group

Description:

Decitabine 20mg/m2 d1-5; Aclacinomycin 10mg/m2 d1-5; Cytarabine 15mg/m2 q12h d1-14; G-CSF 200ug/m2 -12h to d14; Sorafenib 0.4g bid continously at the condition of being naive to sorafenib.

Treatment:

Drug: Ibrutinib