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

NCT ID: NCT05297123

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-03
• Study Completion Date: 2023-12-31

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ATRA/arsenic Group

ATRA 20mg 3 times a day for 8 weeks Arsenic can be given intravenously (ATO) or oral Realgar-Indigo naturalis formula(RIF) ATO 0.15mg/kg/d for 8 weeks (If the total daily amount is greater than 10mg, only 10mg/d can be given) RIF 60 mg/kg/d for 8 weeks The total dose can be appropriately adjusted according to the side-effects of the drug. 4 weeks for 1 course. If the patient has obvious side effects, the treatment should stop for 2 weeks. Each patient will be received at least two courses.

Quality of life assessments are performed every 2 months. After the end of the course of treatment, the condition is mainly evaluated based on the platelet count and bone marrow smear. If the treatment is effective, the above regimen can be continued; if not, the study is withdrawn.

Group Type: EXPERIMENTAL

All-trans retinoic acid

Intervention Type: DRUG

All-trans retinoic acid (ATRA) 20mg 3 times a day for 8 weeks.

Arsenic Trioxide

Intervention Type: DRUG

ATO 0.15mg/kg/d for 8 weeks (If the total daily amount is greater than 10mg, only 10mg/d can be given)

Realgar-Indigo naturalis formula

Intervention Type: DRUG

60 mg/kg/d for 8 weeks

Interventions

All-trans retinoic acid

All-trans retinoic acid (ATRA) 20mg 3 times a day for 8 weeks.

Intervention Type: 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)

Intervention Type: DRUG

Realgar-Indigo naturalis formula

60 mg/kg/d for 8 weeks

Intervention Type: DRUG

Other Intervention Names

ATRA; ATO; RIF

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huaiyu Wang, Dr.

Role: STUDY_CHAIR

First Affiliated Hospital Xi'an Jiaotong University

Locations

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Huaiyu Wang, Dr.

Role: CONTACT

whymed@126.com

008615809207527

Facility Contacts

Huaiyu Wang, Dr.

Role: primary

whymed@126.com

15809207527

References

Bennett DA. How can I deal with missing data in my study? Aust N Z J Public Health. 2001 Oct;25(5):464-9.

Reference Type: BACKGROUND

PMID: 11688629 (View on PubMed)

Dos Santos GA, Kats L, Pandolfi PP. Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia. J Exp Med. 2013 Dec 16;210(13):2793-802. doi: 10.1084/jem.20131121.

Reference Type: BACKGROUND

PMID: 24344243 (View on PubMed)

de The H, Chen Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010 Nov;10(11):775-83. doi: 10.1038/nrc2943. Epub 2010 Oct 22.

Reference Type: BACKGROUND

PMID: 20966922 (View on PubMed)

Zhao Z, Zuber J, Diaz-Flores E, Lintault L, Kogan SC, Shannon K, Lowe SW. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal. Genes Dev. 2010 Jul 1;24(13):1389-402. doi: 10.1101/gad.1940710.

Reference Type: BACKGROUND

PMID: 20595231 (View on PubMed)

El Hajj H, Dassouki Z, Berthier C, Raffoux E, Ades L, Legrand O, Hleihel R, Sahin U, Tawil N, Salameh A, Zibara K, Darwiche N, Mohty M, Dombret H, Fenaux P, de The H, Bazarbachi A. Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells. Blood. 2015 May 28;125(22):3447-54. doi: 10.1182/blood-2014-11-612416. Epub 2015 Mar 23.

Reference Type: BACKGROUND

PMID: 25800051 (View on PubMed)

Other Identifiers

XJTU1AF2019LSK-077

Identifier Type: -

Identifier Source: org_study_id