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

NCT03642236 | Unknown Phase 2 DMC

• 1 other identifier: BTKi in FLT3 mutant AML
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• CR rate

  After the first and second cycle induction

• OS

  2 years

• DFS

  2 years

Study Arms (2)

BTK treatment

EXPERIMENTAL

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.

Drug: Ibrutinib

BTK-free treatment

ACTIVE COMPARATOR

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.

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Ibrutinib 420mg day -3 to d14 combining with chemotherapy with/without sorafenib based on whether the patients are naive to sorafenib before relapse.

BTK treatment; BTK-free treatment

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Guopan Yu

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 22, 2018
• Study Start: August 1, 2018
• Primary Completion: August 1, 2022
• Study Completion: September 1, 2023
• Last Updated: August 22, 2018

Record last verified: 2018-08

Locations

CN (1)