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

Phase 1

Recruiting

• Conditions: P53 Mutation; Myeloid Malignancy; MDS; Aml
• Interventions: Drug: Decitabine; Drug: Arsenic Trioxide

• Registration Number: NCT03855371
• Lead Sponsor: Ruijin Hospital

Brief 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.
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Detailed Description

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. In two independent clinical trials reported recently, DNA demethylating drug Decitabine (DAC) treatment yielded a surprisingly high rate of complete remission (CR) in mp53-expressing myelodysplastic syndromes (MDS) pa...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-12-27
• Study Start: 2018-01-10
• Study First Submitted QC: 2019-02-25
• Study First Posted: 2019-02-26
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-03
• Last Update Posted: 2022-11-04
• Primary Completion: 2023-07
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 5

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Decitabine plus arsenic trioxide	Decitabine	decitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)
Decitabine plus arsenic trioxide	Arsenic Trioxide	decitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

Primary Outcome Measures

Name	Time	Method
side effect	during the whole treatment	evaluate the side effects of current regimen

Secondary Outcome Measures

Name	Time	Method
Overall response rate	at the end of cycle 4 (each cycle is 28 days)	Partial response (PR) + complete response (CR) rate

Trial Locations

Locations (1)

Hematological department, Shanghai Institute of Hematology, Ruijin Hospital; 🇨🇳 Shanghai, Shanghai, China