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

NCT ID: NCT03031249

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-08
• Study Completion Date: 2027-10-15

Brief 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.

Detailed 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.

Conditions

AML

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High Dose of Cytarabine

Patients receive high dose of cytarabine.

Group Type: ACTIVE_COMPARATOR

Cytarabine

Intervention Type: DRUG

Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.

HDAC + ATRA + ATO

Patients receive high dose of cytarabine plus ATRA and ATO treatment.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.

all-trans retinoic acid

Intervention Type: DRUG

ATRA at a dose of 30mg/㎡/d on day 1-14.

Arsenic Trioxide

Intervention Type: DRUG

ATO at a dose of 10mg/d on day 1-14

Interventions

Cytarabine

Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.

Intervention Type: DRUG

all-trans retinoic acid

ATRA at a dose of 30mg/㎡/d on day 1-14.

Intervention Type: DRUG

Arsenic Trioxide

ATO at a dose of 10mg/d on day 1-14

Intervention Type: DRUG

Other Intervention Names

HDAC; ATRA; ATO

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianxiang Wang

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Countries

China

Other Identifiers

IIT2016007（ATO + ATRA）

Identifier Type: -

Identifier Source: org_study_id