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Acute Myeloid LeukemiaPhase 2NCT03381781

Decitabine,Cytarabine and Arsenic Trioxide for Acute Myeloid Leukemia With p53 Mutations

A Phase 2 study testing Decitabine, Arsenic Trioxide and Cytarabine in people with Acute Myeloid Leukemia and P53 Mutation, run by Li Junmin at 3 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a prospective,uncontrolled and multi-institution trial.The aim is to identify if using decitabine,cytarabine and ATO as the therapy of acute myeloid leukemia(AML) with p53 mutations has better relapse free survival and complete response than using decitabine and cytarabine. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Acute Myeloid Leukemia, P53 Mutation
What is being tested?
Decitabine, Arsenic Trioxide and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
3 sitesChina
Study dates
Mar 2018to Nov 2020
Phase
Phase 2
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 elderly AML,AML transferred from MDS,therapy related AML
  • exclude acute promyelocytic leukemia(APL)
  • p53 mutations determined by DNA sequencing from bone marrow
  • 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

  • APL
  • without p53 mutations
  • previously treated elderly AML
  • central nervous system is involved
  • abnormal hepatic function or renal function
  • severe cardiac disease,including myocardial infarction,cardiac dysfunction
Show all 18Show fewer
  • ECG:QTc>0.44 sec in men,QTc>0.46 sec in women
  • with other malignant tumor meanwhile
  • active tuberculosis or HIV-positive patients
  • 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.

Li Junmin, MD contact

0086-21-64370045 ext. 665251

drlijunmin@126.com

China3 sites

  • Ruijin Hospital North

    Shanghai

    Sujiang Zhang, MD, 0086-21-67888761, zbruce.zhang@hotmail.com

    Sujiang Zhang, MD

  • Ruijin Hospital

    Shanghai

    Junmin Li, 021-86-64370045 ext. 665251, drlijunming@126.com

    Junming Li

  • Shanghai Institute of Hematology

    Shanghai

    Min Lu, Ph.D., 86-21-64370045 ext. 610805, min.lu@shsmu.edu.cn

    Min Lu, Ph.D.

Other trials in China

About this study

Official title: Decitabine,Cytarabine(Ara-C) and Arsenic Trioxide(ATO) in the Treatment of Acute Myeloid Leukemia With p53 Mutations

This is a prospective,uncontrolled and multi-institution trial.The aim is to identify if using decitabine,cytarabine and ATO as the therapy of acute myeloid leukemia(AML) with p53 mutations has better relapse free survival and complete response than using decitabine and cytarabine.

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

This study is designed as a model of precision medicine. About 1500 AML patients will be applied for TP53 sequencing. The bone marrow samples will be collected and its p53 status will be Sanger sequenced in 3-5 days before drug administration. The 100 mp53-positive patients will be trialed, while the others (mp53-negative patients) will be subjected to standard treatment or other clinical trials.

In this study,100 patients with p53 mutations will be enrolled,including newly diagnosed AML aged 60-75,AML transferred from Myelodysplastic Syndrome(MDS) and therapy related AML.

Being tested
Decitabine, Arsenic Trioxide, Cytarabine
Keywords
p53 mutation, acute myeloid leukemia, decitabine, Arsenic trioxide, cytarabine
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 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

  • CytarabineDrug

    Also called DNA damaging agent, Ara-C

    15mg/m^2,hypodermic injection,q12h,d1-7

Study groups in NCT03381781
Study groupRoleWhat they receive
Experimental groupExperimentalPatients with p53 mutations will be treated with Decitabine,Arsenic Trioxide and Cytarabine.
Receives: Drug: Decitabine; Drug: Arsenic Trioxide; Drug: Cytarabine

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: From date of complete release until the date of first documented relapse, assessed up to 6-8months

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 posted22 Dec 2017
  2. Study startMar 2018 (estimated)
  3. Primary completionNov 2019 (estimated)
  4. Study completionNov 2020 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03381781
Sponsor's protocol ID
RuijinH mutant p53 AML
Status last verified
Jan 2018
First submitted
21 Nov 2017
Last updated
4 Jan 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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 2 study testing Decitabine, Arsenic Trioxide and Cytarabine in people with Acute Myeloid Leukemia 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 18 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 Jan 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Li Junmin, MD (0086-21-64370045 ext. 665251, drlijunmin@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

relapse free survival (time frame: From date of complete release until the date of first documented relapse, assessed up to 6-8months). 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 NCT03381781, 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 4 Jan 2018.

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