Background
Main text
Targeting FLT3 signaling pathway
FLT3 mutations
FLT3 inhibitors for AML
Sorafenib
Midostaurin
Quizartinib
Gilteritinib
Crenolanib
Ongoing clinical trials utilizing FLT3 inhibitors in AML
Protocol title | NCT identifier |
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Agent: sorafenib | |
Phase I/II study of combination of sorafenib, vorinostat, and bortezomib for the treatment of acute myeloid leukemia with complex- or poor-risk (monosomy 5/7) cytogenetics or FLT3–ITD positive genotype (Sponsors: Millennium Pharmaceuticals, Inc., Bayer, and Merck Sharp & Dohme Corp.) | NCT01534260 |
A pilot study of sorafenib in patients with acute myeloid leukemia as peri-transplant remission maintenance (Sponsor: National Cancer Institute) | NCT01578109 |
Phase I study of the combination of bortezomib and sorafenib followed by decitabine in patients with acute myeloid leukemia (Sponsor: National Cancer Institute) | NCT01861314 |
Agent: midostaurin | |
An open-labeled, multi-center, expanded treatment protocol (ETP) of midostaurin (PKC412) in patients 18 years of age or older with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard induction and consolidation chemotherapy (Sponsor: Novartis Pharmaceuticals) | NCT03114228 |
A phase II, randomized trial of standard of care, with or without midostaurin to prevent relapse following allogeneic hematopoietic stem cell transplantation in patients with FLT3–ITD mutated acute myeloid leukemia (Sponsor: Novartis Pharmaceuticals) | NCT01883362 |
A randomized phase II/III trial of “Novel Therapeutics” versus azacitidine in newly diagnosed patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), age 60 or older LEAP: Intergroup less-intense AML platform trial (Sponsor: National Cancer Institute) | NCT03092674 |
Agent: quizartinib | |
A phase 3 open-label randomized study of quizartinib (AC220) monotherapy versus salvage chemotherapy in subjects with tyrosine kinase 3—internal tandem duplication (FLT3–ITD) positive acute myeloid leukemia (AML) refractory to or relapsed after first-line treatment with or without hematopoietic stem cell transplantation (HSCT) consolidation (Sponsor: Daiichi Sankyo Inc.) | NCT02039726 |
A phase 3, double-blind, placebo-controlled study of quizartinib (AC220) administered in combination with induction and consolidation chemotherapy, and administered as maintenance therapy in subjects 18–75 years old with newly diagnosed FLT3–ITD (+) acute myeloid leukemia (Sponsor: Daiichi Sankyo Inc.) | NCT02668653 |
A phase II single-arm open-labeled study evaluating combination of quizartinib and omacetaxine mepesuccinate (QUIZOM) in newly diagnosed or relapsed/refractory AML carrying FLT3–ITD (Sponsor: The University of Hong Kong) | NCT03135054 |
Agent: gilteritinib | |
A multi-center, randomized, double-blind, placebo-controlled phase III trial of the FLT3 inhibitor gilteritinib administered as maintenance therapy following allogeneic transplant for patients with FLT3/ITD AML (Sponsor: Astellas Pharma Global Development, Inc.) | NCT02997202 |
A phase 3 multicenter, randomized, double-blind, placebo-controlled trial of the FLT3 inhibitor gilteritinib (ASP2215) administered as maintenance therapy following induction/consolidation therapy for subjects with FLT3/ITD AML in first complete remission (Sponsor: Astellas Pharma Global Development, Inc.) | NCT02927262 |
A phase 2/3 multicenter, open-label, 3-arm, 2-stage randomized study of ASP2215 (gilteritinib), combination of ASP2215 plus azacitidine and azacitidine alone in the treatment of newly diagnosed acute myeloid leukemia with FLT3 mutation in patients not eligible for intensive induction chemotherapy (Sponsor: Astellas Pharma Global Development, Inc.) | NCT02752035 |
Agent: crenolanib | |
Pilot study of crenolanib combined with standard salvage chemotherapy in subjects with relapsed/refractory acute myeloid leukemia (Sponsor: Arog Pharmaceuticals, Inc.) | NCT02626338 |
A phase II study of crenolanib besylate maintenance following allogeneic stem cell transplantation in patients with FLT3-positive acute myeloid leukemia (Sponsor: Arog Pharmaceuticals, Inc.) | NCT02400255 |
Phase I–II study of crenolanib combined with standard salvage chemotherapy, and crenolanib combined With 5-azacitidine in acute myeloid leukemia patients with FLT3 activating mutations (Sponsor: Arog Pharmaceuticals, Inc.) | NCT02400281 |
Agent: others | |
First in man study to evaluate the safety, tolerability and preliminary efficacy of the Fc-optimized FLT3 antibody FLYSYN for the treatment of acute myeloid leukemia patients with minimal residual disease (Sponsor: University Hospital Tuebingen) | NCT02789254 |
Phase I open-label, sequential dose escalation study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of SKLB1028 when administered daily to patients with relapsed or refractory acute myeloid leukemia (Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd) | NCT02859948 |
A first-in-human phase 1/2a study to assess the safety, tolerability, efficacy, and pharmacokinetics of FF-10101-01 in subjects with relapsed or refractory acute myeloid leukemia (Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.) | NCT03194685 |
Targeting epigenetics
Epigenetics in AML
Epigenetic mechanisms
Histone acetylation and methylation
DNA methylation and hydroxymethylation
Epigenetic modifiers for AML
Histone deacetylase (HDAC) inhibitors
BET inhibitors
DOT1L inhibitors
LSD1 inhibitors
DNMT inhibitors
IDH inhibitors
Ongoing clinical trials utilizing epigenetic modifiers in AML
Protocol title | NCT identifier |
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Agent: HDAC inhibitors | |
A phase 2 study of temozolomide plus vorinostat in patients with relapse/refractory acute myeloid leukemia (AML) (Sponsor: Stanford University) | NCT01550224 |
Phase I/II study with oral panobinostat maintenance therapy following allogeneic stem cell transplantation in patients with high risk MDS or AML (PANOBEST) (Sponsor: Johann Wolfgang Goethe University Hospital) | NCT01451268 |
A phase 1 study of AZD1775 in combination with belinostat in relapsed and refractory myeloid malignancies and selected untreated patients with acute myeloid leukemia (Sponsor: National Cancer Institute) | NCT02381548 |
A phase I and dose expansion cohort study of panobinostat in combination with fludarabine and cytarabine in pediatric patients with refractory or relapsed acute myeloid leukemia or myelodysplastic syndrome (Sponsor: St. Jude Children’s Research Hospital) | NCT02676323 |
Agent: BET inhibitors | |
A phase 1/2, open-label, dose-escalation, safety and tolerability study of INCB054329 in subjects with advanced malignancies (Sponsor: Incyte Corporation) | NCT02431260 |
A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed, refractory hematologic malignancies (Sponsor: GlaxoSmithKline) | NCT01943851 |
A phase 1 dose escalation, multicenter, open-label, safety, pharmacokinetic and pharmacodynamic study of FT-1101 in patients with relapsed or refractory hematologic malignancies (Sponsor: Forma Therapeutics, Inc.) | NCT02543879 |
A dose escalation study of RO6870810/TEN-010 in patients with acute myeloid leukemia and myelodysplastic syndrome (Sponsor: Hoffmann-La Roche) | NCT02308761 |
A phase 1/2, open-label, dose-escalation, safety and tolerability study of INCB054329 in subjects with advanced malignancies (Sponsor: Incyte Corporation) | NCT02431260 |
Agent: LSD1 inhibitors | |
A phase 1/2, open-label, dose-escalation/dose-expansion, safety and tolerability study of INCB059872 in subjects with advanced malignancies (Sponsor: Incyte Corporation) | NCT02712905 |
A phase I open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK2879552 given orally in subjects with relapsed/refractory acute myeloid leukemia (Sponsor: GlaxoSmithKline) | NCT02177812 |
A multi-center, open label study to assess the safety, steady-state pharmacokinetics and pharmacodynamics of IMG-7289 with and without ATRA (Tretinoin) in patients with advanced myeloid malignancies (Sponsor: Imago BioSciences, Inc.) | NCT02842827 |
Agent: guadecitabine | |
A phase 3, multicenter, randomized, open-label study of guadecitabine (SGI-110) versus treatment choice in adults with previously treated acute myeloid leukemia (Sponsor: Astex Pharmaceuticals) | NCT02920008 |
A phase 3, multicenter, open-label, randomized study of SGI-110 versus treatment choice (TC) in adults with previously untreated acute myeloid leukemia (AML) who are not considered candidates for intensive remission induction chemotherapy (Sponsor: Astex Pharmaceuticals) | NCT02348489 |
A phase Ib study evaluating the safety and pharmacology of atezolizumab (Anti-PD-L1 Antibody) administered in combination with immunomodulatory agents in patients with acute myeloid leukemia (Sponsor: Hoffmann-La Roche) | NCT02892318 |
Agent: IDH inhibitors | |
An open-label, non-randomized, multicenter phase I study to determine the maximum tolerated and/or recommended phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML) (Sponsor: Bayer) | NCT03127735 |
A phase 1, multicenter, open-label, safety study of AG-120 or AG-221 in combination with induction therapy and consolidation therapy in patients with newly diagnosed acute myeloid leukemia with an IDH1 and/or IDH2 mutation (Sponsor: Agios Pharmaceuticals, Inc.) | NCT02632708 |
A phase 3, multicenter, double-blind, randomized, placebo-controlled study of AG-120 in combination with azacitidine in subjects ≥18 years of age with previously untreated acute myeloid leukemia with an IDH1 mutation (Sponsor: Agios Pharmaceuticals, Inc.) | NCT03173248 |
A phase 1/1b, multicenter, open-label, dose-escalation study of FT-2102 as a single agent and in combination with azacitidine in patients with acute myeloid leukemia or myelodysplastic syndrome with an IDH1 mutation (Sponsor: Forma Therapeutics, Inc.) | NCT02719574 |
Targeting BCL-2 and JAK/STAT pathway
Ongoing clinical trials targeting BCL-2 and JAK/STAT pathway in AML
Protocol title | NCT identifier |
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Agent: BCL-2 inhibitors | |
Phase I dose-escalation study of the orally administered selective Bcl-2 Inhibitor S 055746 as monotherapy for the treatment of patients with acute myeloid leukaemia (AML) or high or very high risk myelodysplastic syndrome (MDS) (Sponsor: Institut de Recherches Internationales Servier) | NCT02920541 |
A phase 2a, open-label, dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, and clinical effects of intravenously administered nerofe in subjects with acute myelogenous leukemia or myelodysplastic syndrome (Sponsor: Immune System Key Ltd) | NCT03059615 |
A phase 1b study evaluating the safety, pharmacokinetics and efficacy of venetoclax as a single-agent and in combination with azacitidine in subjects with higher-risk myelodysplastic syndromes after hypomethylating agent-failure (Sponsor: AbbVie) | NCT02966782 |
A phase I and expansion cohort study of venetoclax in combination with chemotherapy in pediatric patients with refractory or relapsed acute myeloid leukemia (Sponsor: St. Jude Children’s Research Hospital) | NCT03194932 |
A randomized, double-blind, placebo controlled study of venetoclax co-administered with low dose cytarabine versus low dose cytarabine in treatment naïve patients with acute myeloid leukemia who are ineligible for intensive chemotherapy (Sponsor: AbbVie) | NCT03069352 |
A randomized, double-blind, placebo controlled phase 3 study of venetoclax in combination with azacitidine versus azacitidine in treatment naïve subjects with acute myeloid leukemia who are ineligible for standard induction therapy (Sponsor: AbbVie) | NCT02993523 |
A phase 1b study of ABT-199 (GDC-0199) in combination with azacitidine or decitabine in treatment-naive subjects with acute myelogenous leukemia who are ≥60 years of age and who are not eligible for standard induction therapy (Sponsor: AbbVie) | NCT02203773 |
Agent: JAK/STAT inhibitors | |
Induction therapy with pacritinib combined with decitabine or cytarabine in older patients with acute myeloid leukemia (AML) (Sponsor: Weill Medical College of Cornell University) | NCT02532010 |
Phase I study of pacritinib and chemotherapy in patients with acute myeloid leukemia and FLT3 mutations (Sponsor: Ohio State University Comprehensive Cancer Center) | NCT02323607 |