A Randomized Phase 2 Trial of ASTX727 +/- Iadademstat in Accelerated/Blast-Phase Philadelphia Chromosome-Negative Myeloproliferative Neoplasms (MPNs)
National Cancer Institute (NCI)
Summary
This phase II trial compares the effect of ASTX727 in combination with iadademstat to ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). ASTX727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with iadademstat may be more effective than ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative MPNs.
Description
PRIMARY OBJECTIVE: I. To compare the acute leukemia response-complete (ALR-C) rate of iadademstat + ASTX727 (35 mg decitabine + 100 mg cedazuridine) and ASTX727 (35 mg decitabine + 100 mg cedazuridine) monotherapy within 4 cycles of therapy in patients with accelerated/blast-phase myeloproliferative neoplasms (MPN-AP/BP) previously untreated with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi). SECONDARY OBJECTIVE: I. To compare event-free survival (EFS), overall survival (OS), and percentage of patients going onto allogeneic hematopoietic stem cell transplant (allo-HCT) of…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have morphologically confirmed diagnosis of Philadelphia-chromosome negative MPN in accelerated-phase (10-19% myeloid blasts) or blast-phase (≥ 20% myeloid blasts) arising from polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, or MPN not otherwise specified, as per the World Health Organization (WHO) 2016 classification OR myelodysplastic syndrome (MDS)/MPN overlap syndromes (e.g., chronic myelomonocytic leukemia \[CMML\]) with ≥ 10% blasts * Patients must not have received prior DNMTi. Previous use of janus kinas…
Interventions
- ProcedureBiospecimen Collection
Undergo buccal swab and blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration and biopsy
- ProcedureBone Marrow Biopsy
Undergo bone marrow aspiration and biopsy
- DrugDecitabine and Cedazuridine
Given PO
- DrugIadademstat
Given PO
Locations (30)
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- Stanford Cancer Institute Palo AltoPalo Alto, California
- UM Sylvester Comprehensive Cancer Center at Coral GablesCoral Gables, Florida
- UM Sylvester Comprehensive Cancer Center at Coral SpringsCoral Springs, Florida
- UM Sylvester Comprehensive Cancer Center at Deerfield BeachDeerfield Beach, Florida