Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS

• Status: Recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Here the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk AML/MDS patients.

About 200 AML/MDS patients will be sequenced for TP53 sequence before recruitment. The investigators estimated about 5 patients, based on the reported p53 mutation frequency in AML/MDS, will be p53-mutated. In the trial, the investigators will selectively recruit the mp53 AML/MDS patients that are predicted to respond to DAC+ATO regimen with highest chance (based on the relevant basic studies).

The investigators designate mutant p53-based clinical trials as 'PANDA (P53 AND Arsenic)-Trials'.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ruijin Hospital
• Treatments: Arsenic Trioxide; Azacitidine; Decitabine

Criteria

Inclusion Criteria:

• Occurrence of p53 mutants that are predicted to respond to ATO+DAC with highest chance

• Patients newly diagnosed with myelodysplastic syndromes.

• ECOG Performance status ≤ 3.

• Aged from 18 to 75.

• Active bone marrow hyperplasia indicated by morphology

• Normal liver and renal function, bilirubin ≤35μmol/L, ASL/ALT lower than 2xULN, creatinine level ≤150μmol/L

• Normal cardiac function

• Written Informed consent.

Exclusion Criteria:

• Patients previously treated.

• Confirmed CNS involvement.

• Abnormal liver function which does not meet the inclusion criteria.

• Severe cardiac diseases including myocardial infarction or heart insufficiency.

• QT interval ≥450ms on ECG.

• With other visceral malignancy.

• Active tuberculosis or HIV(+).

• Patients with pregnancy or lactation.

• Allergic or significantly contraindicated to any drugs involved in intervention.

• Significantly contraindicated to HMA chemotherapy.

• ECOG performance status ≥3, CCI >1, ADL <100.

• Unable to understand or follow the study protocol.

• Previous intolerance or allergy history to similar drugs.

• Aged <18 yrs or >75yrs

• MDS patients previously treated with decitabine.

• Participation at same time in another study in which investigational drugs are used.

• Any other conditions interfering the study.