NCT03855371

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. 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'.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2018

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 27, 2017

Completed
14 days until next milestone

Study Start

First participant enrolled

January 10, 2018

Completed
1.1 years until next milestone

First Posted

Study publicly available on registry

February 26, 2019

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2023

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2024

Completed
Last Updated

November 4, 2022

Status Verified

November 1, 2022

Enrollment Period

5.5 years

First QC Date

December 27, 2017

Last Update Submit

November 3, 2022

Conditions

P53 MutationMyeloid MalignancyMDSAml

Keywords

p53 mutationpersonalized treatmentDecitabineArsenic TrioxideAMLMDS

Outcome Measures

Primary Outcomes (1)

  • side effect

    evaluate the side effects of current regimen

    during the whole treatment

Secondary Outcomes (1)

  • Overall response rate

    at the end of cycle 4 (each cycle is 28 days)

Study Arms (1)

Decitabine plus arsenic trioxide

EXPERIMENTAL

decitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

Drug: DecitabineDrug: Arsenic Trioxide

Interventions

DecitabineDRUG

20mg/m2/d, intravenously, d1-d5, q4w

Also known as: DAC
Decitabine plus arsenic trioxide
Arsenic TrioxideDRUG

0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

Also known as: ATO
Decitabine plus arsenic trioxide

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • Patients previously treated.
  • Confirmed CNS involvement.
  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hematological department, Shanghai Institute of Hematology, Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

DecitabineArsenic Trioxide

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

AzacitidineAza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesArsenicalsInorganic ChemicalsOxidesOxygen Compounds

Study Officials

  • Sujiang Zhang, MD, PhD

    Shanghai Institute of Hematology, Ruijin Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Min Lu, PhD

CONTACT

0086-21-64370045min.lu@shsmu.edu.cn

Sujiang Zhang, MD, PhD

CONTACT

zbruce.zhang@hotmail.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Ph.D.

Study Record Dates

First Submitted

December 27, 2017

First Posted

February 26, 2019

Study Start

January 10, 2018

Primary Completion

July 1, 2023

Study Completion

July 1, 2024

Last Updated

November 4, 2022

Record last verified: 2022-11

Locations

CN(1)