NCT01241500: ONTIME

Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine

Completed Phase 3 Last updated 29 June 2020

What this trial tests

Phase 3 trial testing ON 01910.Na in Myelodysplastic Syndromes in 299 participants. Completed in 3 October 2018.

Timeline

1 November 2010

Primary endpoint
3 October 2018

3 October 2018

Quick facts

Lead sponsor	Traws Pharma, Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	299
Start date	1 November 2010
Primary completion	3 October 2018
Estimated completion	3 October 2018
Sites	87 locations across United States, Belgium, France, Germany, Italy, Spain

Drugs / interventions tested

• ON 01910.Na — full drug profile →

Conditions studied

• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →
• MDS — all drugs for MDS →
• RAEB — all drugs for RAEB →
• Chronic Myelomonocytic Leukemia — all drugs for Chronic Myelomonocytic Leukemia →

Sponsor

Traws Pharma, Inc. — full company profile →

Who can join

18 and older, any sex, with Myelodysplastic Syndromes or MDS. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Overall survival
  Time frame: Up to 18 months
  Overall survival (OS) is defined as the time from randomization to death from any cause. All patients will be followed until death or progression, even if they have discontinued treatment for whatever cause. Patients lost to follow-up will be censored at the time last known alive. The OS primary analysis will compare the active ON 01910.Na regimen to BSC once a total number of 223 deaths has been

Sponsor's own description

The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cell cycle proteins as promising targets in cancer therapy.
   Otto T, Sicinski P. · · 2017 · cited 1412× · PMID 28127048 · DOI 10.1038/nrc.2016.138
2. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
   Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
3. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
   Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
4. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial.
   Garcia-Manero G, Fenaux P, Al-Kali A, Baer MR, et al · · 2016 · cited 134× · PMID 26968357 · DOI 10.1016/s1470-2045(16)00009-7
5. The two sides of chromosomal instability: drivers and brakes in cancer.
   Hosea R, Hillary S, Naqvi S, Wu S, et al · · 2024 · cited 102× · PMID 38553459 · DOI 10.1038/s41392-024-01767-7
6. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress.
   Chapman CM, Sun X, Roschewski M, Aue G, et al · · 2012 · cited 67× · PMID 22351695 · DOI 10.1158/1078-0432.ccr-11-2113
7. Second-Generation Antimitotics in Cancer Clinical Trials.
   Novais P, Silva PMA, Amorim I, Bousbaa H. · · 2021 · cited 37× · PMID 34371703 · DOI 10.3390/pharmaceutics13071011
8. Cyclers' kinases in cell division: from molecules to cancer therapy.
   Milletti G, Colicchia V, Cecconi F. · · 2023 · cited 28× · PMID 37516809 · DOI 10.1038/s41418-023-01196-z