Clinical trial NCT03031249: Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia
Official title: Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: AML
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2017-01-25
Enrollment: 80
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Relapse-Free Survival Rate (RFS)
timeFrame: Within 5 years after randomization
Secondary outcomes:
measure: Non-relapse Mortality
timeFrame: through treatment completion, an average of 5 months
measure: Overall Survival Rate (OS)
timeFrame: Within 5 years after randomization
measure: Cumulative incidence of relapse
timeFrame: Within 5 years after randomization
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Jianxiang Wang
role: PRINCIPAL_INVESTIGATOR
References: