Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies

Table 3 Clinical trials of SMO inhibitors in MF and other hematologic malignancies

Smo inhibitor	Patient population	Phase	Combination partner	Primary endpoint	Status^a	ClinicalTrials.gov identifier
Sonidegib (LDE225)	PMF, post-PV MF, post-ET MF	1/2	Ruxolitinib	DLTs, MTD and/or RP2D (of combination), proportion of patients achieving ≥ 35% decrease in spleen volume	Recruiting	NCT01787552
	Acute leukemias	2		CR, CRi	Recruiting	NCT01826214
	CML	1	Nilotinib	DLT, MTD, RP2D	Recruiting	NCT01456676
PF-04449913	Refractory, resistant, or intolerant select hematologic malignancies	1		DLT	Completed	NCT00953758[109]
	AML/MDS	1/2	Chemotherapy	DLT, CRR, OS	Recruiting	NCT01546038
	Acute leukemias	2	Post–stem cell transplant	Relapse-free survival	Recruiting	NCT01841333
	MDS	2		ORR	Recruiting	NCT01842646
Vismodegib (GDC-0449)	AML/MDS	1b/2		ORR	Recruiting	NCT01880437
	Lymphomas (B cell, CLL)	2		ORR	Recruiting	NCT01944943
	MM	1	Post–stem cell transplant	Change in MM CSC counts	Ongoing, not recruiting	NCT01330173
BMS-833923	CML	1/2	Dasatinib	RP2D for combination	Completed	NCT01218477
BMS-833923	CML	2	Dasatinib	MMR	Ongoing, not recruiting	NCT01357655[89]
	MM	1	Lenalidomide + dexamethasone or bortezomib	DLT, MTD, RP2D	Completed	NCT00884546[110]

AML acute myeloid leukemia, CLL chronic lymphocytic leukemia, CML chronic myeloid leukemia, CR complete remission, CRi complete remission with incomplete blood count recovery, CRR complete response rate, CSC cancer stem cell, DLT dose-limiting toxicity, ET essential thrombocythemia, MDS myelodysplastic syndromes, MF myelofibrosis, MM multiple myeloma, MMR major molecular response, MTD maximum tolerated dose, ORR overall response rate, OS overall survival, PMF primary myelofibrosis, PV polycythemia vera, RP2D recommended phase 2 dose, SMO smoothened.
^aStudy status accessed on November 26, 2013 from ClinicalTrials.gov (http://www.clinicaltrials.gov).

ISSN: 1756-8722