From: Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia
Non ABL-directed Inhibitors | Clinical Study | Drugs Combination | Patient Characteristics (pts) | Results |
---|---|---|---|---|
FT-Is | ||||
Tipifarnib | (42) | – | CP, AP, BP (n = 22) | HR: 27% CP, 4% AP CyR: 18% CP |
PhaseI NCT00040105(43) | IM | CP having ABL KD mutation (n = 25) | HR: 76% CyR: 36% | |
Lonafarnib | Pilot Study(44) | – | CP, AP IM resistant (n = 13) | HR: 8% CP, 8% AP |
PhaseI NCT00047502(45) | IM | CP, AP, BP (n = 23) | HR: 9% CP, 17% AP/BP CyR: 4% CP, 4% AP/BP | |
mTOR-Is | ||||
Rapamycin | PhaseI/II NCT00776373 | Cytarabine Etoposide | AP, BP | NDP |
Everolimus | PhaseI/II NCT00081874 | – | BP | NDP |
PhaseI/II NCT00093639 | IM | CP | NDP | |
BEZ235 | PhaseI NCT01756118 | – | AP, BP | NDP |
Temsirolimus | PhaseI NCT00101088 | IM | AP, BP | NDP |
Smo-As | ||||
LDE225 | PhaseI NCT01456676 | NIL | AP, BP | NDP |
BMS833923 | PhaseI NCT1218477(66) | DAS | CP, AP, BP (n = 27) | CyR: 4% CP PA/BP: no responded |
PhaseI NCT01357655 | DAS | CP | No participants were enrolled | |
PF-04449913 | Phase I NCT00953758 | – | CP | Safety, Pharmacokinetics and Pharmacodynamics study |
JAK2-Is | ||||
Ruxolitinib | PhaseI NCT01702064 | NIL | CP | ongoing |
PhaseI/II NCT02253277 | NIL | CP, Ph + ALL | ongoing | |
PhaseI/II NCT01751425 | – | CP with MRD | ongoing | |
PhaseI/II NCT01914484 | NIL | AP, BP, Ph + ALL | ongoing | |
PhaseI/II NCT02973711 | NIL | CP | ongoing | |
Hsp90-Is | ||||
17-AAG | PhaseI NCT00093821 | – | BP | NDP |
PhaseI NCT00098423 | Cytarabine | BP | NDP | |
STA-9090 | PhaseI NCT00964873 | – | BP | NDP |
PhaseI NCT00858572 | – | refractory or relapsed CML | NDP | |
HDAC-Is | ||||
Vorinostat | PhaseI NCT00275080 | Decitabine | BP | NDP |
PhaseI NCT00816283 | DAS | AP, BP | NDP | |
PhaseI NCT00278330 | Flavopiridol | BP | NDP | |
LBH589 | Phase II/III NCT00451035(91) | – | CML TKIs resistant (n = 29) | HR: 3% |
PhaseI NCT00686218 | IM | CP with MRD | NDP | |
BCL2-Is | ||||
Obatoclax | PhaseI NCT00438178 | – | BP | NDP |
AURK-Is | ||||
MK-0457 | Phase I/II(108) | – | AP, BP, Ph + ALL All with T315I (n = 18) | HR: 39% AP/BP CyR: 5% Ph + ALL |
PhaseII NCT00405054(110) | – | AP, BP, Ph + ALL All with T315I (n = 52) | CyR: 8% CP, 6% AP/BP HR: 4% CP | |
PhaseI NCT00500006 | DAS | CP | No Data Results Posted | |
PHA-739358 | PhaseI(113) | – | AP, BP (n = 29) | HR: 7% AP/BP, 7% Ph + ALL CyR: 3% AP/BP, 3% Ph + ALL MR: 3% Ph + ALL |
AT9283 | PhaseI NCT00522990 | – | CP, AP, BP | NDP |
XL288 | PhaseI NCT00464113 | – | CP, AP, BP, Ph + ALL | NDP |
PT-Is | ||||
Omacetaxine | PhaseII(120) | – | CP, TKIs resistant (n = 46) | HR: 67%, CyR: 22 |
PhaseI/II(121) | – | CP, previously exposed to TKIs (n = 81) | HR: 81%, CyR: 20% | |
PhaseII NCT00375219(122) | – | CP, BCR-ABL1 T315I mutant (n = 62) | HR: 77%, CyR: 22% |