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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