P53 MutationPhase 1PANDA-T0NCT03855371
Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS
A Phase 1 study testing Decitabine and Arsenic Trioxide in people with P53 Mutation and Myeloid Malignancy, run by Ruijin Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- P53 Mutation, Myeloid Malignancy, MDS
- What is being tested?
- Decitabine and Arsenic Trioxide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 10 Jan 2018to Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Sujiang Zhang, MD, PhD contact
China1 site, 1 recruiting
- Recruiting
Hematological department, Shanghai Institute of Hematology, Ruijin Hospital
Shanghai, Shanghai Municipality, 200025
Min Lu, PhD, 0086-21-64370045 ext. 610805, min.lu@shsmu.edu.cn
Sujiang Zhang, PhD, zbruce.zhang@hotmail.com
About this study
Official title: Combination of Decitabine and ATO to Treat AML/MDS Expressing a Classified Type of Mutant p53
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'.
Read the 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) patients and acute myeloid leukemia (AML) patients. Notably, all of the mp53-expressing patients in the two clinical studies, despite of CR, relapsed quickly. This was attributed to a failure in thoroughly clearing all leukemia-specific mutations and the preexisting mp53 subclone outgrew in all of the relapse patients. Indeed, The investigators also found p53 dysfunctional cells quickly develop a DAC resistance mechanism in cultured tissue (unpublished data). Meanwhile, the investigators found arsenic trioxide (ATO) selectively inhibit p53-mutated cells involving mutant p53 reactivation and mutant p53 degradation (presumably mediated by upregulated mdm2 and RCHY1/Pirh2 through reactivated mutant p53). In addition, DAC and ATO show synergy in inhibiting p53-mutated cells.
In current phase I trial, the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk MDS patients. About 200 AML/MDS patients will be recruited for TP53 sequencing before being trialed. The investigators estimated about 50 patients, based on p53 mutation frequency in AML/MDS, will be sequenced to be mp53-positive. The mp53-positive AML/MDS patients are known to have an extremely poor prognosis. The investigators will select high-risk mp53 MDS patients that are predicted to respond to DAC+ATO with highest chance based on our relevant basic studies.
The other participants (free of p53 mutation) will be excluded from the trial.
- Conditions
- P53 Mutation, Myeloid Malignancy, MDS, Aml
- Being tested
- Decitabine, Arsenic Trioxide
- Keywords
- p53 mutation, personalized treatment, Decitabine, Arsenic Trioxide, AML, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called DAC
20mg/m2/d, intravenously, d1-d5, q4w
Arsenic TrioxideDrug
Also called ATO
0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Decitabine; Drug: Arsenic Trioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
side effect
evaluate the side effects of current regimen
Measured: during the whole treatment
Secondary outcomes (1)
Overall response rate
Partial response (PR) + complete response (CR) rate
Measured: at the end of cycle 4 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start10 Jan 2018
- Primary completionJul 2023 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for P53 MutationStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Min Lu, Ruijin Hospital
- Investigators
- Sujiang Zhang, MD, PhD, Principal investigator, Shanghai Institute of Hematology, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03855371
- Sponsor's protocol ID
- Mutant p53-based trial
- Acronym
- PANDA-T0
- Status last verified
- Nov 2022
- First submitted
- 27 Dec 2017
- Last updated
- 4 Nov 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Decitabine and ATO to Treat AML/MDS Expressing a Classified Type of Mutant p53
- ClinicalTrials.gov ID
- NCT03855371
- Acronym / sponsor ID
- PANDA-T0 / Mutant p53-based trial
- Conditions
- P53 Mutation, Myeloid Malignancy, MDS, Aml
- Keywords
- p53 mutation, personalized treatment, Decitabine, Arsenic Trioxide, AML, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 10 Jan 2018 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 26 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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'.
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) patients and acute myeloid leukemia (AML) patients. Notably, all of the mp53-expressing patients in the two clinical studies, despite of CR, relapsed quickly. This was attributed to a failure in thoroughly clearing all leukemia-specific mutations and the preexisting mp53 subclone outgrew in all of the relapse patients. Indeed, The investigators also found p53 dysfunctional cells quickly develop a DAC resistance mechanism in cultured tissue (unpublished data). Meanwhile, the investigators found arsenic trioxide (ATO) selectively inhibit p53-mutated cells involving mutant p53 reactivation and mutant p53 degradation (presumably mediated by upregulated mdm2 and RCHY1/Pirh2 through reactivated mutant p53). In addition, DAC and ATO show synergy in inhibiting p53-mutated cells.
In current phase I trial, the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk MDS patients. About 200 AML/MDS patients will be recruited for TP53 sequencing before being trialed. The investigators estimated about 50 patients, based on p53 mutation frequency in AML/MDS, will be sequenced to be mp53-positive. The mp53-positive AML/MDS patients are known to have an extremely poor prognosis. The investigators will select high-risk mp53 MDS patients that are predicted to respond to DAC+ATO with highest chance based on our relevant basic studies.
The other participants (free of p53 mutation) will be excluded from the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine plus arsenic trioxide | Experimental | Drug: Decitabine, Drug: Arsenic Trioxidedecitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DAC20mg/m2/d, intravenously, d1-d5, q4w | Drug | Decitabine plus arsenic trioxide |
| Arsenic TrioxideAlso: ATO0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d) | Drug | Decitabine plus arsenic trioxide |
Primary outcome
side effect
Time frame: during the whole treatment
evaluate the side effects of current regimen
1 secondary outcome
Overall response rate
Time frame: at the end of cycle 4 (each cycle is 28 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sujiang Zhang, MD, PhD contact
Sujiang Zhang, MD, PhD principal investigator
Shanghai Institute of Hematology, Ruijin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Decitabine and Arsenic Trioxide in people with P53 Mutation and Myeloid Malignancy, run by Ruijin Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Min Lu, PhD (0086-21-64370045 ext. 610805, min.lu@shsmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
side effect (time frame: during the whole treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.