Table 2.
New BCR-ABL and NON BCR-ABL targeted therapeutic approaches for CML patients.
| Drugs | Molecular target of the drugs | Indications or efficacy | Clinical Trials Number |
|---|---|---|---|
| BCR-ABL targeted therapy | |||
| Asciminib (ABL001) | BCR-ABL1 Kinase | Resistance or failure to TKI Monotherapy/combination | NCT03595917 (Phase I) |
| The combination therapy is promising in patients with T315I mutation | NCT03578367 (Phase II with Imatinib) | ||
| NCT03595917 (Phase I with Dasatinib) | |||
| NCT02081378 (Phase I with Nilotinib) | |||
| NCT03106779 (Phase III with Bosutinib) | |||
| Olverembatinib (HQP1351) | BCR-ABL1 | Resistance or failure to TKI | NCT03883087 (Phase II) |
| Is efficacious in patients with T315I and other mutations | NCT03883100 (Phase II) | ||
| Vodobatinib (K0706) | BCR-ABL1 | Resistance or failure to ≥ 3TKIs, except for patients carrying BCR-ABL T315I mutation | NCT02629692 (phase I/II) |
| PF-114 | BCR-ABL1 | Resistance or failure to ≥2GTKI | NCT02885766 (phase I/II) |
| Is efficacious in patients with T315I mutations and other resistant mutations in BCR-ABL | |||
| NON BCR-ABL targeted therapy | |||
| Tipifarnib or Zarnestra (R115777) | Farnesyl transferase | Resistance or failure to TKI | NCT00040105 (phase I) |
| Lonafarnib (SCH66336) | NCT00047502 (phase I) | ||
| NCT00038597 (phase II) | |||
| Rapamycin | mTOR | Resistance or failure to TKI | NCT00776373 (phase I/II) |
|
Everolimus |
In combination with DNA damaging agent etoposide |
NCT00081874 (phase I/II) |
|
| NCT00093639 (phase I) | |||
| Ruxolitinib | JAK2/STAT5 | Resistance disease to eradicate the LSCs. In combination with Nilotinib in advanced or resistant disease | NCT01702064 (phase I) |
| NCT02253277 (phase I) | |||
| In combination with conventional TKIs and TFR | NCT03654768 (phase II) | ||
| NCT03610971 (phase II) | |||
| Panobinostat (LBH589) | Histone deacetylase | Resistance or failure to TKI | NCT00449761(phase II) |
| NCT00451035 (phase II) | |||
| Tozasertib (MK0457) | Aurora kinase and BRC-ABL | Resistance or failure to TKI | NCT00405054 (phase II) |
| Is efficacious in patients with T315I | NCT00500006 (phase I) | ||
| Danusertib (PHA-739358) | Activity against BCR kinase including the gatekeeper T315I mutant | The European Clinical Trails | |
| Data Base (EudraCT number 2007-004070-18). | |||
| Pioglityazone | PPARgamma | Resistance disease to eradicate the LSCs. | NCT02888964 (phase II) |
| In combination with Imatinib is promising and TFR | EudraCT 2009-011675-79 | ||
| NCT02889003 (phase II) | |||
| Decitabine | DNA | Resistance or failure to TKI | NCT01498445 Phase I/II |
| Have effects both with monotherapy or combined with imatinib | NCT00042016 Phase II | ||
| NCT00054431 Phase II | |||
| Omacetaxine | Protein synthesis | Resistance to ≥ 2 TKIs | NCT00462943 (phase II) |
| Monotherapy in patients with BCR-ABL T315I mutation | NCT02078960 (Phase I/II) | ||
| NCT00375219 (phase II) | |||