Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia

AML Clinical Trial

Official title:

Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03031249
• Other study ID #: IIT2016007-EC-1-2
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 8, 2017
• Est. completion date: December 2022

Study information

• Verified date: March 2020
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Lijun Liu
• Phone: 86-22-23909237
• Email: bloodgcp[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this open-label, randomized, prospective clinical trial, nucleophosmin-1(NPM1) mutated acute myeloid leukemia (AML) patients who have reached CR are randomized into two groups.The control group receive high-dose cytarabine(HDAC) regimen while the experimental group receive high dose of cytarabine plus tretinoin(ATRA) and arsenic trioxide(ATO) treatment.The safety and efficacy of ATRA and ATO is evaluated.

Description:

In this open-label, randomized, prospective clinical trial, NPM1- mutated AML patients who have reached CR are randomized into two groups.

In experimental group, patients receive cytarabine at a dose of 3g/㎡/d on the first, third and fifth day, ATRA at a dose of 30mg/㎡/d on day 1-14 and ATO at a dose of 0.15mg/kg/d (maximum, 10mg/d) on day 1-14. Patients in control group only receive high dose of cytarabine.

The safety and efficacy of ATRA plus ATO regimen is evaluated.The primary outcome is relapse-free survival rate after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Age of 14 to 55 years old;

2. Patients that meet the diagnostic criteria(WHO 2008 criteria) of AML (except APL subtypes) and with NPM1-mutated.

3. Reached CR after induction regimen.

4. ECOG score of = 2;

5. Patients with eligible laboratory examination including liver,renal and heart function.

6. Adult patients are willing to participate in the study and sign the informed consent by themselves or by their immediate family. Patients under 18 years old willing to participate should have their legal guardians sign the informed consent.

Exclusion Criteria:

1. Secondary leukemia.

2. Patients had other tumor at active stage or had received radiotherapy or chemotherapy in the last 6 months due to other tumor.

3. Patients with other blood diseases(for example, haemophiliacs) are excluded.However, patients with abnormal blood count, but with undiagnosed MDS or MPD patients are included.

4. Acute panmyelosis with myelofibrosis and myeloid sarcoma patients;

5. With BCR-ABL fusion gene;

6. Pregnant or lactating women;

7. With ineligible renal or liver function;

8. With active cardiovascular disease;

9. Severe infection disease including uncured tuberculosis pulmonary aspergillosis;

10. AIDS;

11. Patients had central nervous system involvement when they were diagnosed as AML.

12. Patients with epilepsy or dementia or other mental disease who couldn't understand or follow the research.

13. Drugs, medical, mental or social situation may distract patients from following the research or being evaluated the results.

14. Patients with other factors which were considered unsuitable to participate in the study by the investigators.

Related Conditions & MeSH terms

• AML
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Cytarabine
Cytarabine at a dose of 3g/?/d on the first, third and fifth day.
• all-trans retinoic acid
ATRA at a dose of 30mg/?/d on day 1-14.
• Arsenic Trioxide
ATO at a dose of 10mg/d on day 1-14

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse-Free Survival Rate (RFS)	RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for NPM1 mutated leukemia patients who achieve CR.	Within 5 years after randomization
Secondary	Non-relapse Mortality		through treatment completion, an average of 5 months
Secondary	Overall Survival Rate (OS)		Within 5 years after randomization
Secondary	Cumulative incidence of relapse		Within 5 years after randomization