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Table 1 Clinical studies and results from non ABL-directed Inhibitors

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%
  1. FT-Is Farnesyl Transferase Inhibitors, mTOR-Is mammalian Target of Rapamycin, Smo-As Smo Antagonists, JAK2-Is JAK2 Inhibitors, Hsp-90-Is Hsp-90 Inhibitors, HDAC-Is HDAC Inhibitors, BCL2-Is BCL2 Inhibitors, AURK-Is Aurora Kinase Inhibitors, PT-Is Protein Translation Inhibitors, HR Hematological Remission, CyR Cytogenetic Remission, CP Chronic Phase, AP Accelerated Phase, BP Blast Phase, NDP No Data Posted, MRD Minimal Residual Disease