A trial investigating the use of danvatirsen monotherapy followed by a combination with venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) is set to begin soon. 

This phase 1 study will assess the merits of this therapeutic strategy in terms of safety and efficacy. Danvatirsen is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3. Venetoclax is a commercially available, potent, selective small molecule inhibitor of BCL-2 (a protein that has antiapoptotic properties found on some cancer cells). 

Researchers plan to recruit 24 participants for the trial, with patients enrolled in cohorts of 3. Participants must be 18 years of age or older and have a confirmed diagnosis of MDS or AML according to World Health Organization (WHO) diagnostic criteria. Patients with active, uncontrolled infection or active central nervous system leukemia are excluded from the trial. In addition, they must not have had major surgery or be on any concurrent anticancer therapy or investigational drug within 14 days before the start of the study. 

In the first phase of the study, participants will be administered danvatirsen monotherapy. Researchers will assess the results in the first cohort before deciding whether to administer higher doses, maintain the current dose, or de-escalate dosing for future cohorts. One cycle of treatment is planned to be approximately 4 weeks (28 days) long.

Read more about MDS etiology 

For the next phase of the study, patients will be administered danvatirsen in combination with 400 mg of venetoclax orally once per day. The research team will determine up to 2 dose levels of danvatirsen based on the first phase of the study. For the venetoclax dose, researchers plan to escalate to the stated goal dose day by day (for example, 100 mg on day 1, 200 mg on day 2, and finally, 400 mg on day 3). This is to mitigate the risk of tumor lysis syndrome. 

The primary outcome measure of this study will be response to therapy (overall response rate) from 21 days after the study start date to within 14 days following the administration of treatment. Secondary outcome measures include duration of response, event-free/overall survival, and 30- and 60-day all-cause mortality. 

The study has an estimated start date in August 2023, an estimated primary completion date in March 2025, and an estimated study completion date set for December 2027. 


Danvatirsen monotherapy followed by combination with venetoclax in relapsed/refractory MDS & AML. ClinicalTrials.gov. Published August 14, 2023. Accessed August 18, 2023.