Table 3.
Selected clinical trials with FLT3 inhibitors in patients with untreated AML.
| Regimen | Phase | N |
FLT3-mut (pts) |
Clinical activity | Toxicity | Notes |
|---|---|---|---|---|---|---|
| Nonrandomized trials | ||||||
| Sorafenib (BAY43-9006) + induction (7 + 3) and consolidation (ida/Ara-C) CT [68] | II | 51 | 15 | CR: 38 pts (75%); FLT3-mut: 14 pts (93%), FLT3-WT: 24 pts (66%) (p = 0.033) | ↑LFTs, Gl, dermatological | Pts < 65 years |
| Sunitinib (SU11248) + induction (7 + 3) and consolidation (Ara-C) CT [74] | I–ll | 10 | 10 | CR/CRi: 7 pts (70%) PR: 1 pt (10%) | Cytopenias, infection, Gl, hypertension, bleeding | Pts ≥ 60 years |
| Lestaurtinib (CEP-701) [80] | II | 27 | 5 | ≥ 50% ↓ BM blasts: FLT3-WT: 5 pts (23%) Disappearance of PB blasts: FLT3-mut: 3 pts (60%) | Gl, fatigue, elevated alkaline phosphatase | Short time to progression; pts ≥ 60 yrs |
| Midostaurin (PKC412) + induction (7 + 3) and consolidation (Ara-C) CT [92] | lb | 40 | 13 | CR: 32 pts (80%); FLT3-mut: 12 pts (92%), FLT3-WT: 20 pts (74%) OS @1 yr: FLT3-mut: 85%, FLT3-WT: 81 % | Gl (more with 100 mg dose) | Response rates are with PKC 50 mg bid; pts ≤ 60 yrs |
| Tandutinib (MLN518) + induction (7 + 3) and consolidation (Ara-C) CT [95] | l–ll | 15 | 5 of 29 total pts | CR: 11 pts (73%) | Gl | Dose amendments due to Gl toxicity; results are from 1 5 pts on 200 mg b.i.d. continuously or days 1-14 |
| Randomized trial | ||||||
| Sorafenib (BAY43-9006) + induction (7 + 3) and consolidation (Ara-C) CT vs CT alone [69] | II | 197 | 28 | CR: Sorafenib + CT: 49 pts (48%), CT alone: 57 pts (60%) CRi: Sorafenib + CT: 9 pts (8.8%), CT alone: 4 pts (4.2%) OS: Sorafenib + CT: 13 mo, CT alone: 15 mo | Pneumonia, sepsis, Gl, dermatologic | Pts > 60 years; no difference in EFS or OS |
AML: Acute myelogenous leukemia; Ara-C: Cytarabine; b.i.d.: Twice a day; BM: Bone marrow; CR: Complete response; CRi: Complete response with incomplete blood count recovery; CT: Chemotherapy; EFS: Event-free survival; FLT3: FMS-like tyrosine kinase 3; FLT3-mut: FLT3-mutated; FLT3-WT: FLT3-wild type; GI: Gastrointestinal; Ida: Idarubicin; LFT: Liver function tests; N: Evaluable patients for efficacy; OS: Overall survival; PB: Peripheral blood; PR: Partial response; Pts: Patients.