Table.1.
Selected Ongoing Clinical Trials of Small Molecular Inhibitors in Patients with Acute Myeloid Leukemia
| Molecular Target | Small Molecule Inhibitor |
Phase of the study |
Study Design |
ClinicalTrials.gov Identifier |
|---|---|---|---|---|
| Aurora kinase | Alisertib (Aurora A Kinase inhibitor) |
Phase 1 | alisertib in combination with 7+3 induction chemotherapy | NCT01779843 |
| AMG 900 | Phase 1 | Single agent | NCT01380756 | |
| Farnesyl transferase | Lestaurtinib | Phase 1/ 2 | lestaurtinib + cytarabine + idarubicin relapsed and refractory AML | NCT00469859 |
| Histone deacetylase | Valproic acid | Phase 1/ 2 | ATRA+ Valproic acid+ low dose cytarabine | NCT00995332 |
| Entinostat (MS275) |
Phase 2 | Entinostat + 5AZC in elderly | NCT01305499 | |
| Vorinostat | Phase 2 | Temozolomide + vorinostat in patients more than 60 years old with newly diagnosed or relapsed or refractory AML | NCT01550224 | |
| Vorinostat | Phase 3 | Cytarabine + daunorubicin hydrochloride or idarubicin+ cytarabine with or without vorinostat | NCT01802333 | |
| Proteasome inhibitors | Bortezomib | Phase 2 | Comparing decitabine with decitabine + subcutaneously injected bortezomib in untreated AML | NCT01420926 |
| Ixazomib | Phase 2 | Single agent for NPM1c relapsed/ refractory AML | NCT02030405 | |
| CXCR4 | Plerixafor | Phase 1 | Plerixafor+ decitabine for induction and post-remission therapy in elderly | NCT01352650 |
| Plerixafor | Phase 1/2 | Plerixafor+ GCSF + chemotherapy in refractory or relapsed AML | NCT00906945 | |
| BL-8040 | Phase 2A, multicenter, open-label | Single agent therapy for relapsed and refractory AML | NCT01838395 | |
| BMS-936564 (Anti-CXCR4) | Phase 1, multicenter, open-label | Single agent in relapsed AML, and B cell malignancies | NCT01120457 | |
| HSP90 | Ganetespib | Phase 1/2 | To combine either the tyrosine kinase inhibitor AC220, plerixafor, or ganetespib with chemotherapy in older patients with AML and high-risk myelodysplastic syndrome (AML18 Pilot) | NCT01236144 |
| FLT3 | Crenolanib | Phase 2 | Single agent therapy in relapsed and refractory AML with FLT3- D835 activating mutation | NCT01522469 |
| Sorafenib | Phase 1/2 | Sorafenib + vorinostat, + bortezomib for AML with complex or poor-risk (monosomy 5/7) cytogenetics or FLT3-ITD–positive mutation | NCT01534260 | |
| Sorafenib | Phase 1 | Single agent maintenance therapy after allogeneic stem cell transplantation. | NCT01398501 | |
| Sorafenib | Phase 3 | Bortezomib+ sorafenib for de novo AML with high allelic ratio FLT3-ITD disease | NCT01371981 | |
| Midostaurin (PKC412) |
Phase 2 | Single agent therapy for c-kit or FLT3-ITD mutated t(8;21) AML | NCT01830361 | |
| c-kit | Nilotinib | Phase 1/2 | Nilotinib+ mitoxantrone, etoposide +high-dose cytarabine (NOVE-HiDAC) induction chemotherapy followed by consolidation therapy for poor-risk patients up to 65 years old with c-kit positive AML | NCT01222143 |
| Hedgehog pathway | PF-04449913 | Phase 2 | Single agent therapy for high risk AML post-allogeneic stem cell transplantation relapse | NCT01841333 |
| WNT pathway | PRI-724 | Phase 1/2 | Single agent tharpy for advanced malignancies. | NCT01606579 |
| CWP232291 | Phase 1 | Single agent therapy for relapsed and refractory AML, chronic myelomonocytic leukemia, myelodysplastic syndrome or high-risk myelofibrosis | NCT01398462 | |
| IDH1/2 | AG-120 | Phase 1 | Monotherapy in advanced hematological malignancies with IDH1 mutation | NCT02074839 |
| AG-221 | Phase 1 | Monotherapy in advanced hematological malignancies with IDH2 mutation | NCT01915498 | |
AML, Acute myeloid leukemia; 5AZC, 5-Azacytidine.