NCT03377725

Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)

Withdrawn Phase 3 Last updated 16 August 2023

What this trial tests

Phase 3 trial testing Decitabine in Myelodysplastic Syndromes. Withdrawn.

Timeline

20 March 2018

Primary endpoint
31 March 2018

31 March 2018

Quick facts

Lead sponsor	Li Junmin
Phase	Phase 3
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Start date	20 March 2018
Primary completion	31 March 2018
Estimated completion	31 March 2018
Sites	3 locations across China

Drugs / interventions tested

• Decitabine (decitabine) — full drug profile →
• Arsenic Trioxide (ARSENIC TRIOXIDE) — full drug profile →

Conditions studied

• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →
• P53 Mutation — all drugs for P53 Mutation →

Sponsor

Li Junmin

Who can join

Adults 18 to 75, any sex, with Myelodysplastic Syndromes or P53 Mutation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

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 Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished).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'.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.