Dasatinib Combined With Chemotherapy in Relapsed t(8;21) Acute Myeloid Leukemia With KIT D816 Mutation

Sponsor

Institute of Hematology & Blood Diseases Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03560908

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this multi-center, open-label, no control,prospective clinical trial, a total of 30 relapsed acute myeloid leukemia with t(8;21) translocation and KIT D816 mutation patients will be enrolled. Dasatinib 70 mg twice a day will be administrated for two weeks from day 1 of re-induction chemotherapy. The purpose of current study is to determine the clinical efficacy and tolerability of combination therapy of dasatinib with multi-agent chemotherapy in relapsed acute myeloid leukemia with t(8;21) translocation and KIT D816 mutation.

Condition or Disease	Intervention/Treatment	Phase
Relapsed AML T(8;21) C-KIT Mutation	Drug: Dasatinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dasatinib Combined With Multi-agents Chemotherapy in Relapsed t(8;21) Acute Myeloid Leukemia With KIT D816 Mutation

Actual Study Start Date :

Jul 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib plus chemotherapy Dasatinib combined with chemotherapy for relapsed t(8;21) AML with D816 mutation	Drug: Dasatinib Dasatinib 70mg twice a day will be administered orally for 2 weeks along with re-induction chemotherapy from day 1 of chemotherapy. Recommended re-induction regimens include (1)FLAG: Fludarabine 30mg/m2/d,d1-5;cytarabine 1g-2g/m2/d,d1-5;±G-CSF;(2)IA/DA:idarubicin 8-12mg/m2/d,d1-3 or daunorubicin 45-60mg/m2/d，d1-3;cytarabine 100-200mg/m2/d，d1-7;(3)CAG:Aclarubicin 20mg/d,d1-4；cytarabine 15mg/m2/Q12h,d1-14; ±G-CSF.The chemotherapy regimen is not limited to recommended regimens. Patients will be recommended to receive allogeneic hematopoietic stem cell transplantation (HSCT) once complete remission is achieved. Otherwise, they will continue the consolidation chemotherapy.

Arm

Intervention/Treatment

Experimental: Dasatinib plus chemotherapy

Dasatinib combined with chemotherapy for relapsed t(8;21) AML with D816 mutation

Drug: Dasatinib

Dasatinib 70mg twice a day will be administered orally for 2 weeks along with re-induction chemotherapy from day 1 of chemotherapy. Recommended re-induction regimens include (1)FLAG: Fludarabine 30mg/m2/d,d1-5;cytarabine 1g-2g/m2/d,d1-5;±G-CSF;(2)IA/DA:idarubicin 8-12mg/m2/d,d1-3 or daunorubicin 45-60mg/m2/d，d1-3;cytarabine 100-200mg/m2/d，d1-7;(3)CAG:Aclarubicin 20mg/d,d1-4；cytarabine 15mg/m2/Q12h,d1-14; ±G-CSF.The chemotherapy regimen is not limited to recommended regimens. Patients will be recommended to receive allogeneic hematopoietic stem cell transplantation (HSCT) once complete remission is achieved. Otherwise, they will continue the consolidation chemotherapy.

Outcome Measures

Primary Outcome Measures

composite complete remission (CR) rate [8 weeks]
confirmed rate of complete remission (CR) plus complete remission with incomplete blood count(CRi)

Secondary Outcome Measures

mortality during induction chemotherapy [30 days]
all deaths from start of chemotherapy
post relapsed overall survival [2 years]
2 years overall survival from the date of relapse
overall survival [5 years]
5 years overall survival from the date of diagnosis
post relapsed disease free survival [2 years]
2 years disease free survival from the date of new complete remission

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

T(8;21)acute myeloid leukemia patients with KIT D816 mutation diagnosed by bone marrow morphology, immunology, molecular genetics. The diagnosis and classification are according to WHO 2016 criteria.
Conform to relapsed diagnosis.Only morphological relapsed cases will be enrolled.Molecular relapsed and isolated extramedullary relapsed cases are not eligible.
Age is not limited. Both male and female are eligible.
Eastern Cooperative Oncology Group performance status (ECOG-PS):0-2 point.
Informed consent form must be signed by patients themselves before enrolled for patients aged 18 years or older. Informed consent form must be signed by the legal guardian for patients younger than 18 years.

Exclusion Criteria:

Patients with other blood diseases at the same time (such as haemophilia, primary myelofibrosis and so on) are not considered suitable.
Isolated extramedullary relapsed leukemia.
With other malignant tumors accompanied with AML and needed treatment. 4 .Patients who are unsuitable for the trial considered by investigators.