search
Back to results

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

Primary Purpose

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

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Ibrutinib
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for FLT3-ITD Mutation

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept 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)

Sites / Locations

  • Department of Hematology,Nanfang Hospital, Southern Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BTK treatment

BTK-free treatment

Arm 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.

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.

Outcomes

Primary Outcome Measures

CR rate
OS
DFS

Secondary Outcome Measures

Full Information

First Posted
August 20, 2018
Last Updated
August 20, 2018
Sponsor
Nanfang Hospital, Southern Medical University
search

1. Study Identification

Unique Protocol Identification Number
NCT03642236
Brief Title
Combination of BTK Inhibitor Overcomes Drug-resistance in Refractory/Relapsed FLT3 Mutant AML
Official Title
Combination of Brutons Tyrosine Kinase (BTK) Inhibitor Overcomes Drug-resistance in Refractory/Relapsed FLT3 Mutant Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2018 (Anticipated)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nanfang Hospital, Southern Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
FLT3-ITD Mutation, Acute Myeloid Leukemia, Brutons Tyrosine Kinase

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
122 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BTK treatment
Arm Type
Experimental
Arm 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.
Arm Title
BTK-free treatment
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Description
Ibrutinib 420mg day -3 to d14 combining with chemotherapy with/without sorafenib based on whether the patients are naive to sorafenib before relapse.
Primary Outcome Measure Information:
Title
CR rate
Time Frame
After the first and second cycle induction
Title
OS
Time Frame
2 years
Title
DFS
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guopan Yu
Organizational Affiliation
Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology,Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs