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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Relapsed AML; T(8;21); C-KIT Mutation
• Intervention / Treatment: Drug: Dasatinib

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • HBDH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Conform to relapsed diagnosis.Only morphological relapsed cases will be enrolled.Molecular relapsed and isolated extramedullary relapsed cases are not eligible.
3. Age is not limited. Both male and female are eligible.
4. Eastern Cooperative Oncology Group performance status (ECOG-PS):0-2 point.
5. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite complete remission (CR) rate	confirmed rate of complete remission (CR) plus complete remission with incomplete blood count(CRi)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality during induction chemotherapy	all deaths from start of chemotherapy	30 days
post relapsed overall survival	2 years overall survival from the date of relapse	2 years
overall survival	5 years overall survival from the date of diagnosis	5 years
post relapsed disease free survival	2 years disease free survival from the date of new complete remission	2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 15, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: relapse; mutation; dasatinib; leukemia,myeloid, acute; KIT
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: IHBDH-IIT2018004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No