CLINICAL TRIAL UPDATES
A look at ongoing clinical trials in myeloid malignancies
PHASE III TRIALS
Controlled Study of Rigosertib Versus Physician ’ s Choice of Treatment in MDS Patients After Failure of an HMA ( NCT02562443 ) estimated study completion date : September 2018 estimated enrollment : 225 sponsor : Onconova Therapeutics , Inc . In a previous study , ONTIME , the multikinase inhibitor rigosertib did not improve survival , compared with conventional care , for patients with myelodysplastic syndromes ( MDS ) for whom hypomethylating agents ( HMAs ) failed ( median survival = 8.2 months for rigosertib vs . 5.9 months for supportive care with or without low-dose cytarabine ; p = 0.33 ). However , patients who were primary-refractory to HMAs seemed to fare better with rigosertib in a subset analysis . The INSPIRE study has a similar design to the ONTIME trial , but enriches for higher-risk patients with no or transient responses to HMAs .
A Phase III , Multicenter , Randomized , Open-Label Study of Guadecitabine ( SGI-110 ) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia ( NCT02920008 ) estimated study completion date : June 2019 estimated enrollment : 404 sponsor : Astex Pharmaceuticals This multicenter study will compare the next-generation HMA guadecitabine with physician ’ s choice ( including a variety of high- or low-intensity chemotherapeutic regiments ), or best supportive care alone in adults with previously treated acute myeloid leukemia ( AML ). Guadecitabine was granted orphan drug status by the U . S . Food and Drug Administration ( FDA ) in 2015 .
Azacitidine With or Without Nivolumab or Midostaurin , or Decitabine and Cytarabine Alone in Treating Older Patients With Previously Untreated AML or High-Risk MDS ( NCT03092674 ) Estimated primary completion date : June 2022 estimated enrollment : 1,670 sponsor : National Cancer Institute This randomized phase II / III trial will evaluate azacitidine-based regimens for the treatment of older patients with previously untreated AML or high-risk MDS : azacitidine with or without nivolumab or midostaurin , and azacitidine with or without decitabine plus cytarabine . These combinations are intended to stop the growth of cancer cells by interfering with the ability of cells to grow and spread by blocking some of the enzymes needed for cell growth .
A Study of ASP2215 ( Gilteritinib ), Administered as Maintenance Therapy Following Induction / Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 ( FLT3 / ITD ) AML in First Complete Remission ( NCT02927262 ) estimated study completion date : March 2024 estimated enrollment : 354 sponsor : Astellas Pharma , Inc . This randomized , parallel-assignment , double-blind study will compare relapse-free survival ( RFS ) in patients with AML and FLT3 / ITD mutations in first complete remission treated with either gilteritinib ( a novel oral FLT3 / AXL inhibitor ) or placebo . Earlier trials demonstrated that FLT3 inhibition with gilteritinib improved survival in patients with FLT3-mutated relapsed / refractory AML .
Study of Iomab-B Prior to HCT Versus Conventional Care in Older Subjects With Active , Relapsed , or Refractory AML ( NCT02665065 ) estimated primary completion date : April 2018 estimated enrollment : 150 sponsor : Actinium Pharmaceuticals In this randomized , open-label study , iomab-B , an anti-CD45 antibody conjugated to the radioisotope iodine 131 , in combination with a reduced-intensity conditioning regimen , is being compared with conventional care as a preparatory regimen for patients with AML undergoing alloHCT . Iomab-B may facilitate alloHCT by selectively ablating bone marrow and destroying CD45-expressing leukemia cells and host immune system cells .
PHASE II TRIALS
A Two-Arm Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Patients With MDS After Failure of HMA-Based Therapy ( NCT02452346 ) estimated study completion date : March 2021 estimated enrollment : 80 sponsor : Weill Medical College of Cornell University Tosedostat , an oral inhibitor of aminopeptidase that influences cellular protein clearance , has demonstrated activity in relapsed / refractory AML . This investigator-sponsored study will examine its efficacy in patients with MDS who have relapsed or are refractory to HMAs . Patients will be enrolled in two arms : patients with low- and intermediate-risk disease and patients with very high-risk disease .
A Study Evaluating Venetoclax in Combination With Azacitidine Compared With Azacitidine Alone in Participants With Previously Untreated Higher-Risk MDS ( NCT02942290 ) estimated study completion date : May 2022 estimated enrollment : 90 sponsor : AbbVie , Inc . The BCL2 inhibitor venetoclax has demonstrated single-agent activity in relapsed / refractory AML and synergistic activity with HMAs in preclinical studies , and is FDA-approved for chronic lymphocytic leukemia . This randomized , phase II , dose-ranging study will compare the safety , pharmacokinetic profile , and efficacy of azacitidine with or without venetoclax in patients with treatment-naïve , higher-risk MDS .
A Biomarker-Directed Phase II Trial of SY-1425 in Patients With AML or MDS ( NCT02807558 ) estimated study completion date : August 2019 estimated enrollment : 100 sponsor : Syros Pharmaceuticals
10 Focus on Myeloid Malignancies