Summary of clinical trials using FLT3-TKI as single agent
| TKI . | Trial (FLT3 status) . | Dosage (MTD) . | Best response . | Duration of response . | Side effects/DLT . | Comment . |
|---|---|---|---|---|---|---|
| Midostaurin (PKC412) | Phase 249 (FLT3 mut only) | Oral, 75 mg, 3×/d | Blasts BM < 50%: 6/20 | 72-330 d | Nausea, pulmonary events | Sustained responses in some patients |
| Blasts PB < 50%: 14/20 | ||||||
| Lestaurtinib (CEP-701) | Phase1/251 (FLT3 mut only) | Oral, 60 mg 2×/d | Blasts PB < 50%: 5/14 | 2 wk-3 mo | Nausea, emesis, diarrhea | Sustained responses in some patients |
| Phase 252 (FLT3 mut + wt, age > 70 y) | Oral, 60-80 mg 2×/d | Blasts PB < 50%: FLT3-mut: 3/5 FLT3-wt: 5/22 | 2 wk-9 mo | |||
| Sorafinib (BAY 43-9006) | Phase 154 (FLT3 mut + wt) | Oral 400 mg BID (range: 200-400 mg 2×/d) | Blast response in PB: FLT3-ITD: 6/6, FLT3-wt: 3/7, FLT3-TKD: 0/3 | ND | Pleural effusion, nausea, vomiting, rash | 1000-fold more selective for FLT3-ITD |
| Semaxanib (SU5416) | Phase 257 (FLT3 mut + wt) | Intravenous, 145 mg/m2 2×/wk | PR: 2/33, HI: 1/33 | 3-3.5 mo | Fatigue, headache, bone pain | AE likely caused by hyperosmolaric drug formulation |
| Phase 259 (AML, FLT3 ND) | Intravenous, 145 mg/m2 2×/wk | Blasts PB and BM < 50%: 7/25 with 1 MR | 1.6 mo (1-5 mo) | |||
| Sunitinib (SU11248) | Phase 161 (FLT3 mut + wt) | Oral, 50 mg 1×/d | Blasts PB and BM <50%: FLT3-ITD: 4/4 (1 HI) FLT3-wt: 2/7 | 4-16 wk | Hypertension (DLT), fatigue, edema | |
| Tandutinib (MLN-518) | Phase 162 (FLT3 mut + wt) | Oral, 50-700 mg 2×/d | NA | NA | Muscular weakness, fatigue, nausea, vomiting | Muscular weakness caused by inhibition of a muscle-type nicotinic receptor at high concentrations |
| Phase 263 (FLT3-ITD only) | Oral, 525mg 2×/d | 6/18 responder: blast decrease in PB and BM | 1-3 mo | |||
| KW-2449 | Phase 164 (FLT3 mut + wt) | Oral, 500 mg 2×/d | Blasts PB and BM < 50% in 26% | ND | Vomiting, nausea, fatigue | Trial closed on basis of PD studies (MTD not reached) |
| AC220 | Phase 167 (FLT3 mut + wt) | Oral, 200 mg 1×/d (range: 12-300 mg/d) | CR: 12% PR: 18% FLT3-ITD: 56% FLT3-wt: 19% | 14 wk | QTc prologation (DLT), peripheral edema, GI events |
| TKI . | Trial (FLT3 status) . | Dosage (MTD) . | Best response . | Duration of response . | Side effects/DLT . | Comment . |
|---|---|---|---|---|---|---|
| Midostaurin (PKC412) | Phase 249 (FLT3 mut only) | Oral, 75 mg, 3×/d | Blasts BM < 50%: 6/20 | 72-330 d | Nausea, pulmonary events | Sustained responses in some patients |
| Blasts PB < 50%: 14/20 | ||||||
| Lestaurtinib (CEP-701) | Phase1/251 (FLT3 mut only) | Oral, 60 mg 2×/d | Blasts PB < 50%: 5/14 | 2 wk-3 mo | Nausea, emesis, diarrhea | Sustained responses in some patients |
| Phase 252 (FLT3 mut + wt, age > 70 y) | Oral, 60-80 mg 2×/d | Blasts PB < 50%: FLT3-mut: 3/5 FLT3-wt: 5/22 | 2 wk-9 mo | |||
| Sorafinib (BAY 43-9006) | Phase 154 (FLT3 mut + wt) | Oral 400 mg BID (range: 200-400 mg 2×/d) | Blast response in PB: FLT3-ITD: 6/6, FLT3-wt: 3/7, FLT3-TKD: 0/3 | ND | Pleural effusion, nausea, vomiting, rash | 1000-fold more selective for FLT3-ITD |
| Semaxanib (SU5416) | Phase 257 (FLT3 mut + wt) | Intravenous, 145 mg/m2 2×/wk | PR: 2/33, HI: 1/33 | 3-3.5 mo | Fatigue, headache, bone pain | AE likely caused by hyperosmolaric drug formulation |
| Phase 259 (AML, FLT3 ND) | Intravenous, 145 mg/m2 2×/wk | Blasts PB and BM < 50%: 7/25 with 1 MR | 1.6 mo (1-5 mo) | |||
| Sunitinib (SU11248) | Phase 161 (FLT3 mut + wt) | Oral, 50 mg 1×/d | Blasts PB and BM <50%: FLT3-ITD: 4/4 (1 HI) FLT3-wt: 2/7 | 4-16 wk | Hypertension (DLT), fatigue, edema | |
| Tandutinib (MLN-518) | Phase 162 (FLT3 mut + wt) | Oral, 50-700 mg 2×/d | NA | NA | Muscular weakness, fatigue, nausea, vomiting | Muscular weakness caused by inhibition of a muscle-type nicotinic receptor at high concentrations |
| Phase 263 (FLT3-ITD only) | Oral, 525mg 2×/d | 6/18 responder: blast decrease in PB and BM | 1-3 mo | |||
| KW-2449 | Phase 164 (FLT3 mut + wt) | Oral, 500 mg 2×/d | Blasts PB and BM < 50% in 26% | ND | Vomiting, nausea, fatigue | Trial closed on basis of PD studies (MTD not reached) |
| AC220 | Phase 167 (FLT3 mut + wt) | Oral, 200 mg 1×/d (range: 12-300 mg/d) | CR: 12% PR: 18% FLT3-ITD: 56% FLT3-wt: 19% | 14 wk | QTc prologation (DLT), peripheral edema, GI events |
MTD indicates maximum tolerated dose; DLT, dose-limiting toxicity; ND, not determined; NA, not applicable; PB, peripheral blood; BM, bone marrow; PR, partial response; CR, complete response (PR and CR as defined by IWG criteria); MR, morphologic response (clearance of PB blasts and < 5% BM blasts); and HI, hematologic improvement.