DCHA as Postremission Therapy for AML With t(8;21)

Decitabine in Combination With Chidamide, Homoharringtonine and Ara-c (DCHA) as Postremission Therapy for Acute Myeloid Leukemia With t(8;21) :A Multicenter Prospective Study

Acute myelocytic leukemia ( AML) is a highly heterogeneous group of malignant hematopathy. Chromosomal translocation with t (8; 21) (q22; q22) , about 10 ~ 15% incidence in AML and 40% incidence in the AML-M2 type of leukemia, is a karyotype that is considered to have a good prognosis. The National Comprehensive Cancer Network (NCCN) guidelines recommend that high-dose Ara-c regimens may benefit for patients, but with 30 to 40% relapse and serious risks on myelosuppression, infection and bleeding in high-dose Ara-c consolidation chemotherapy and more than 70% recurrence rate with （tyrosine kinase）KIT mutation. So the exploration of a relatively safe and efficient consolidation therapy is one of the difficult problems to be solved in the treatment of mitigatory t (8; 21) AML.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy
• Intervention / Treatment: Drug: Chemotherapy

Detailed Description

Treatment regimen

HA:

homoharringtonine 2mg IV d1-5 cytarabine( Ara-C) 1500mg/m2(<60 year old) ; 1000mg/m2(>60 year old) IV q12h

DCHA:

Decitabine 20mg/m2 d8-12 Chidamide 30mg twice/week P.O. for two weeks per cycle (four doses totally) cytarabine( Ara-C) 1500mg/m2(<60 year old) ; 1000mg/m2(>60 year old) IV q12h d1,3,5 homoharringtonine 2mg IV d10-14

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Li-Xin Wang, MD. Ph.D.; Phone Number: 010-66957676; Email: wanglixin1991@sohu.com
• Study Contact Backup: Name: Li Yu, MD. Ph.D.; Phone Number: 010-66957678; Email: chunhuiliy@yahoo.com

Study Locations

• China
  • Beijing, China, 100853
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Li Yu, M.D. Ph.D.; Phone Number: 86-010-55499003; Email: chunhuiliyu@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Written informed consent provided.

  • The patients were diagnosed AML-M2 with t(8;21) (q22;q22) chromosomal changes and positive acute myeloid leukemia(AML1)-eight twenty one(ETO) fusion gene according to the 2008 World Health Organization (WHO) diagnostic criteria for malignant myeloid diseases.
  • Males or females aged ≥18 years, < 65 years.
  • Eastern Cooperative Oncology Group（ECOG） performance status 0-3.
  • Life expectancy ≥3 months.
  • The morphology was Complete remission (CR) or Cri after 2 cycles of anthracycline induced chemotherapy.
  • No serious disease with heart, lung, liver and kidney.
  • The ability to understand and be willing to sign the Informed Consent Form of the experiment.
  • Patient who can start the investigational therapy within 3-6 weeks after the complete resection
  • Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
  • Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
  • Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

• Known allergic to prior treatment with drugs contained by the trial programme or with a chemical structure similar medicine.
• Pregnancy, breast-feeding women and childbearing age patients who do not want to take contraceptive measures.
• Active serious infection.
• Patients with extramedullary lesions.
• Patients who use drugs or drink alcohol for a long time to influence the evaluation of results.
• Patients with mental illness or other conditions are unable to obtain knowledge and consent, and can not cooperate with the requirements of the completion of the test treatment and examination steps.
• Patients with a history of the clinical significance of Q and T interval（QTc） prolongation (male > 450ms, female >470ms), ventricular tachycardia (VT), atrial fibrillation (AF), degree of heart block, muscle infarction (MI) within 1 years, congestive heart failure (CHF), with symptoms and drug therapy in patients with coronary heart disease.
• Patients with abnormal liver function (total bilirubin > 1.5 x ULN, ALT/AST > 2.5 x ULN, or liver invasion ALT/AST > 5x ULN ), renal function abnormality (serum creatinine > 1.5 x ULN).
• The researchers decided that patient was not appropriate to take part in the experiment.

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: t(8;21)AML; chemotherapy 5-Aza-2'-deoxycytidine IV 20mg/m2 d8-12 homoharringtonine IV 2mg d1-5 chidamide P.O. 30mg twice/W cytarabine IV 1000mg/m2(<60 year old) 500mg/m2(>60 year old) IV q12h d1,3,5	Drug: Chemotherapy; chidamide, decitabine, homoharringtonine, cytarabine; Other Names: DCHA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	To evaluate the disease progression free survival of DCHA as postremission therapy for acute myeloid leukemia with t(8;21) . Progression free survival (PFS)- defined as the time from remission for the first time to the first documented disease progression.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS)- defined as the length of time from trial treatment to death.	2 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Li Yu, MD. Ph.D, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: February 23, 2018
• First Submitted That Met QC Criteria: March 1, 2018
• First Posted (Actual): March 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: AML, chidamide, decitabine
• Other Study ID Numbers: 301-XYK-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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