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

August 20, 2018 updated by: yuguopan, Nanfang Hospital of Southern Medical University

Combination of Brutons Tyrosine Kinase (BTK) Inhibitor Overcomes Drug-resistance in Refractory/Relapsed FLT3 Mutant Acute Myeloid Leukemia (AML)

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

122

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BTK treatment
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
Ibrutinib 420mg day -3 to d14 combining with chemotherapy with/without sorafenib based on whether the patients are naive to sorafenib before relapse.
Active Comparator: BTK-free treatment
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
Ibrutinib 420mg day -3 to d14 combining with chemotherapy with/without sorafenib based on whether the patients are naive to sorafenib before relapse.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
CR rate
Time Frame: After the first and second cycle induction
After the first and second cycle induction
OS
Time Frame: 2 years
2 years
DFS
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital of Southern Medical University

Investigators

  • Principal Investigator: Guopan Yu, Nanfang Hospital of Southern Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2018

Primary Completion (Anticipated)

August 1, 2022

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

August 20, 2018

First Submitted That Met QC Criteria

August 20, 2018

First Posted (Actual)

August 22, 2018

Study Record Updates

Last Update Posted (Actual)

August 22, 2018

Last Update Submitted That Met QC Criteria

August 20, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BTKi in FLT3 mutant AML

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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