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

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Invitation-only; Phase 2; Phase 1

Conditions: AML

Treatments: Drug: all-trans retinoic acid; Drug: Cytarabine; Drug: Arsenic Trioxide

Study type: Interventional

Funder types: Other

Identifiers

NCT03031249

IIT2016007（ATO + ATRA）

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 14 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 2 patient groups

High Dose of Cytarabine

Active Comparator group

Description:

Patients receive high dose of cytarabine.

Treatment:

Drug: Cytarabine

HDAC + ATRA + ATO

Experimental group

Description:

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

Treatment:

Drug: Arsenic Trioxide

Drug: Cytarabine

Drug: all-trans retinoic acid