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Myelodysplastic SyndromesPhase 3NCT03377725

Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)

A Phase 3 study testing Decitabine and Arsenic Trioxide in people with Myelodysplastic Syndromes and P53 Mutation, run by Li Junmin at 3 sites in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a prospective,controlled and multi-institution trial.The aim is to identify if using decitabine and Arsenic Trioxide(ATO) as the therapy of Myelodysplastic Syndrome(MDS) has better relapse free survival and complete response than using decitabine alone. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Myelodysplastic Syndromes, P53 Mutation
What is being tested?
Decitabine and Arsenic Trioxide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesChina
Study dates
20 Mar 2018to 31 Mar 2018
Phase
Phase 3
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

  • de novo MDS
  • The Revised International Prognostic Scoring System(IPSS-R) is intermediate,poor or very poor
  • 18-75years old(including 18-year-old and 75-year-old patients)
  • ECOG<3,CCI≤1,ADL≥100
  • bone marrow is active
  • normal hepatic function and renal function
  • normal cardiac function
  • obtain informed consent

Who cannot join

  • previously treated MDS patients
  • abnormal hepatic function or renal function
  • severe cardiac disease,including myocardial infarction,cardiac dysfunction
  • ECG:QTc>0.44 sec in men,QTc>0.46 sec in women
  • with other malignant tumor meanwhile
  • active tuberculosis or HIV-positive patients
Show all 15Show fewer
  • woman who are pregnant or breastfeeding
  • allergic to any drug in protocol or with contraindications
  • hypomethylation agent(HMA) is contraindicated
  • ECOG≥3,CCI>1,ADL<100
  • cannot understand or obey the protocol
  • with a history of allergies or intolerability
  • with a history of decitabine therapy
  • participate in other clinical trials meanwhile
  • any situations that hinder trial existed

Trial locations and contacts

3 sites in 1 country.

China3 sites

  • Ruijin Hospital North

    Shanghai

  • Ruijin Hospital

    Shanghai

  • Shanghai Institute of Hematology

    Shanghai

Other trials in China

About this study

Official title: Decitabine and Arsenic Trioxide(ATO) in the Treatment of Myelodysplasic Syndrome

This is a prospective,controlled and multi-institution trial.The aim is to identify if using decitabine and Arsenic Trioxide(ATO) as the therapy of Myelodysplastic Syndrome(MDS) has better relapse free survival and complete response than using decitabine alone.

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Particularly, p53 mutation is associated with extremely poor prognosis in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients.

Read more

Decitabine (DAC) is a FDA approved drug for MDS treatment. In two independent clinical trials reported recently, DNA demethylating drug DAC treatment yielded a surprisingly high rate of complete remission (CR) in mp53-harboring AML/MDS patients (Welch, NEJM, 2016; Chang, BJH, 2017). Notably, all of the mp53-expressing patients in the two clinical studies relapsed quickly.

Arsenic trioxide (ATO) is a FDA approved drug for M3-AML treatment. Despite of the observed efficacy in treating non-APL patients, ATO is not yet approved for non-APL cancer treatment. ATO plays key role in regulating both wild-type p53 (wtp53) and mp53. Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished). Our unpublished data also suggests a key role of ATO in regulating mp53 (Lu, The 17th International p53 Workshop, 2017). ATO is widely reported to be able to degrade and thus inhibit mp53's oncogenic function (Hamadeh, BBRC, 1999)(Liu, Blood, 2003). ATO suppressed cancer cell growth by targeting mp53 for degradation by Pirh2 degradation pathway (Yang, JBC, 2011; Yan, PLOS one, 2014);

Here we explore the potential of combination of DAC and ATO in improving the mp53-harboring AML/MDS patients' relapse free survival (RFS) and the ability to thoroughly eliminate mp53 subclone. Basic researches aiming to explore the mechanisms how mp53 cells responds to DAC and/or ATO treatment and how mp53 cells develop resistance to DAC and/or ATO will be coupled. We designate trials aiming for a better treatment regimen for mp53 patients as 'PANDA-Trials'.

Read the detailed description

300 MDS patients will be recruited for trial. They will be randomly administrated with ATO + decitabine (n=200) or decitabine alone (n=100). The RSF, CR ratio, overall survival will be compared between the two arms. Importantly, TP53 status will be sequenced and its correlation with RSF, CR ratio, overall survival within the two arms will be investigated.

Being tested
Decitabine, Arsenic Trioxide
Keywords
Myelodysplastic Syndromes, Decitabine, Arsenic Trioxide, P53 Mutations
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

    Also called DNA demethylation agent, DNA damaging agent

    20mg/m^2,d1-5,ivgtt,28days as a duration

  • Arsenic TrioxideDrug

    Also called As2O3, Arsenic

    0.16mg/kg,d1-5,ivgtt,28days as a duration

Study groups in NCT03377725
Study groupRoleWhat they receive
Experimental groupExperimentalMDS patients of the experimental group will be treated with decitabine and arsenic trioxide.
Receives: Drug: Decitabine; Drug: Arsenic Trioxide
Controlled groupActive comparatorMDS patients of the controlled group will be treated with decitabine alone.
Receives: Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. relapse free survival

    since a patient first being determined as complete release until relapse

    Measured: up to 6-8 months after complete release

Secondary outcomes (2)

  1. complete release

    the percent of patients with complete release in all patients enrolled

    Measured: 2-4 months since the first cycle of treatment

  2. overall survival

    from first diagnosed to death whichever the cause is

    Measured: primary estimated for 1year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2017
  2. Study start20 Mar 2018
  3. Primary completion31 Mar 2018
  4. Study completion31 Mar 2018

Why it stopped: No patient was involved.

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03377725
Sponsor's protocol ID
RuijinH mutant p53 MDS
Status last verified
Jan 2018
First submitted
13 Dec 2017
Last updated
16 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Chang CK, Zhao YS, Xu F, Guo J, Zhang Z, He Q, Wu D, Wu LY, Su JY, Song LX, Xiao C, Li X. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes. Br J Haematol. 2017 Feb;176(4):600-608. doi: 10.1111/bjh.14455. Epub 2016 Dec 16.

    PubMed 27984642

  • Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon B, Lee YS, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036. doi: 10.1056/NEJMoa1605949.

    PubMed 27959731

  • Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler BM, Middleton MR, Siebold C, Jones EY, Sviderskaya EV, Cebon J, John T, Caballero OL, Goding CR, Lu X. Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer Cell. 2013 May 13;23(5):618-33. doi: 10.1016/j.ccr.2013.03.013. Epub 2013 Apr 25.

    PubMed 23623661

  • Lu M, Muers MR, Lu X. Introducing STRaNDs: shuttling transcriptional regulators that are non-DNA binding. Nat Rev Mol Cell Biol. 2016 Aug;17(8):523-32. doi: 10.1038/nrm.2016.41. Epub 2016 May 25.

    PubMed 27220640

  • Lu M, Zak J, Chen S, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X. A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway. Cell. 2014 May 22;157(5):1130-45. doi: 10.1016/j.cell.2014.05.006.

    PubMed 24855949

  • Yan W, Jung YS, Zhang Y, Chen X. Arsenic trioxide reactivates proteasome-dependent degradation of mutant p53 protein in cancer cells in part via enhanced expression of Pirh2 E3 ligase. PLoS One. 2014 Aug 12;9(8):e103497. doi: 10.1371/journal.pone.0103497. eCollection 2014.

    PubMed 25116336

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Decitabine and Arsenic Trioxide in people with Myelodysplastic Syndromes and P53 Mutation, run by Li Junmin at 3 sites 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 15 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: withdrawn, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

relapse free survival (time frame: up to 6-8 months after complete release). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03377725, which also lists 6 linked publications.

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 16 Aug 2023.

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