Acute Myeloid Leukemia
Conditions
Keywords
Acute myeloid leukemia, All-trans Retinoic Acid, Arsenic
Brief summary
The clinical trial was designed to prove that Arsenic plus ATRA possibly had an effect on improving the symptoms, reducing the early mortality rate and prolonging the total survival time of patients with newly diagnosed or relapsed AML.
Detailed description
Acute myeloid leukemia (AML) is a genetically heterogeneous disease with a highly variable prognosis and an overall high mortality rate. The 5-year overall survival of adult AML patients is less than 50%, and only 20% of elderly patients survive over 2 years. Acute promyelocytic leukemia (APL) accounts for 10% - 15% of acute myeloid leukemia. Arsenic and ATRA are very effective treatments for APL, a distinct AML subtype characterized by the expression of the PML/RARA fusion protein. PML/RARA expression disrupts PML NBs and blunts p53 signaling, which contributes to increased self-renewal of myeloid progenitors. The application of all-trans retinoic acid (ATRA) and arsenic modifies APL from highly fatal to highly curable. Both RA and arsenic induce degradation of PML/RARA through distinct pathways. Nucleophosmin-1(NPM1) is the most frequently mutated gene in acute myeloid leukemia (AML). According to El Hajj's research, RA or arsenic trioxide synergistically induces proteasomal degradation of mutant NPM1 in AML cell lines or primary samples, leading to differentiation and apoptosis. Combined ATRA/arsenic treatment significantly reduced bone marrow blasts in 3 AML patients and restored the subnuclear localization of both NPM1 and PML. Overall, there is no consensus yet as to whether the addition of ATRA/arsenic improves the outcome of patients with NPM1 mutant AML. However, it still needs clinical research to confirm. The investigators design a clinical trial to prove that arsenic plus ATRA is possibly improving the symptoms of AML patients, reduce early mortality, and extending overall survival time.
Interventions
DRUGAll-trans retinoic acid
All-trans retinoic acid (ATRA) 20mg 3 times a day for 8 weeks.
DRUGArsenic Trioxide
ATO 0.15mg/kg/d for 8 weeks (If the total daily amount is greater than 10mg, only 10mg/d can be given)
60 mg/kg/d for 8 weeks
Sponsors
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed or relapsed AML.Diagnosis based on Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia(not APL)(2018) * Older than 18 years old * Patients or their families signed written informed consent
Exclusion criteria
* Be allergic to the drug ingredient, the supplementary material or the allergic constitution person * Cardiac insufficiency, renal insufficiency, significant arrhythmias, EKG abnormalities or other important organ dysfunction * Combined with other malignant tumors * Pregnant and lactating women * Participants in other drug trials in the last 3 months * Suffering from mental illness or other circumstances which unable to carry out the plan * Other patients who were not suitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early death rate (ED) | 30 days | Death reported within the first month of diagnosis |
| Overall survival (OS) | From date of enrollment until the date of death from any cause, assessed up to 3 years | the time from enrolled to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic complete remission (HCR) | 30 days | Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0×10\^9 /L; platelet count \>100× 10\^9 /L. |
| Cumulative relapse rate | From the date of enrollment to the date of relpase proved by bone marrow test, assessed up to 3 years | — |
Countries
China
Contacts
Primary ContactHuaiyu Wang, Dr.
Outcome results
None listed