NCT01926587

A Phase I/II, Multi-center, Dose-escalating Study of the Tolerability, Pharmacokinetics, and Clinical Activity of the Combined Administration of Oral Rigosertib With Azacitidine in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

Completed Phase 1/Phase 2 Last updated 15 June 2021

What this trial tests

Phase 1/Phase 2 trial testing oral rigosertib in Myelodysplastic Syndrome in 45 participants. Completed in 16 February 2021.

Timeline

1 August 2013

Primary endpoint
8 December 2020

16 February 2021

Quick facts

Lead sponsor	Traws Pharma, Inc.
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	45
Start date	1 August 2013
Primary completion	8 December 2020
Estimated completion	16 February 2021
Sites	13 locations across United States, France

Drugs / interventions tested

• oral rigosertib — full drug profile →
• Azacitidine (azacitidine) — full drug profile →

Conditions studied

• Myelodysplastic Syndrome — all drugs for Myelodysplastic Syndrome →
• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →
• 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 Syndrome or Acute Myeloid Leukemia. 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.

• Dose escalation part of study: Number of patients in whom Dose a Limiting Toxicity (DLT) are observed
  Time frame: 28 days
  Dose Limiting Toxicity is defined as Grade 3 or greater non-hematological toxicity or stomatitis and/or esophagitis/dysphagitis lasting longer than 3 days.
• Dose escalation part of study: Number of patients in whom adverse events are observed
  Time frame: Up to 48 weeks
  Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
• In Phase 2 of study: Number of patients in whom adverse events are observed
  Time frame: Up to 48 weeks
  Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
• In Phase 2 of study: Area Under the Curve (AUC)
  Time frame: Day 1 and Day 15
  The following time points will be used to collect samples to determine the AUC on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.
• In Phase 2 of the study: Cmax
  Time frame: Days 1 and 15.
  The following time points will be used to collect samples to determine the Cmax on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.

Sponsor's own description

This study, is a Phase I/II clinical trial in three parts: Phase I Dose Escalation, Phase II, Part 1 RPTD Cohort, and Phase II, Part 2 Expansion. The first two parts have been completed. The Phase II, Part 2 Expansion will assess if treatment with rigosertib in combination with azacitidine, has measurable effects in patients with myelodysplastic syndrome (MDS). Safety of patients is an objective throughout all parts of the study.

Publications & conference data

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

1. 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
2. Clinical development of demethylating agents in hematology.
   Navada SC, Steinmann J, Lübbert M, Silverman LR. · · 2014 · cited 107× · PMID 24382388 · DOI 10.1172/jci69739
3. 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
4. Current challenges and unmet medical needs in myelodysplastic syndromes.
   Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. · · 2021 · cited 67× · PMID 34045662 · DOI 10.1038/s41375-021-01265-7
5. Update on rational targeted therapy in AML.
   Shafer D, Grant S. · · 2016 · cited 62× · PMID 26972558 · DOI 10.1016/j.blre.2016.02.001
6. The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?
   Ghelli Luserna di Rorà A, Martinelli G, Simonetti G. · · 2019 · cited 40× · PMID 31771633 · DOI 10.1186/s13045-019-0808-4
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. Emerging treatment options for patients with high-risk myelodysplastic syndrome.
   Bewersdorf JP, Carraway H, Prebet T. · · 2020 · cited 24× · PMID 33240476 · DOI 10.1177/2040620720955006