NCT05297123

Treatment of Acute Myeloid Leukemia With Arsenic and All-trans Retinoid Acid

Treatment of Acute Myeloid Leukemia With Arsenic and All-trans Retinoid Acid (ATRA)

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	All-trans retinoic acid	All-trans retinoic acid (ATRA) 20mg 3 times a day for 8 weeks.
DRUG	Arsenic Trioxide	ATO 0.15mg/kg/d for 8 weeks (If the total daily amount is greater than 10mg, only 10mg/d can be given)
DRUG	Realgar-Indigo naturalis formula	60 mg/kg/d for 8 weeks

Timeline

• Start date: 2019-02-03
• Primary completion: 2023-12-03
• Completion: 2023-12-31
• First posted: 2022-03-28
• Last updated: 2022-03-28

Locations

1 site across 1 country: China