Table 2.
Ongoing trials.
| Drug | Trial; # of patients (n); status | NCT ID | Patients/Treatment | Outcome measures |
|---|---|---|---|---|
| Sorafenib | A pilot study of Sorafenib as peri-transplant remission maintenance; n = 45; active, not recruiting | NCT01578109 | Patients ≥19 years with FLT3-ITD+ AML in CR/PR who plan on undergoing HSCT are given Sorafenib ≥30 days after completion of induction until 4 days before conditioning and within 120 days after HSCT for up to 2 years until progression or unacceptable toxicity | Primary: toxicity Secondary: change in FLT3 suppression and MRD, incidence of NRM and relapse, DFS, OS and pharmacodynamics parameters of Sorafenib |
| Phase I/II study of sorafenib added to busulfan and fludarabine conditioning in patients with relapsed/refractory AML undergoing transplantation; n = 74; recruiting |
NCT03247088 | Patients 18–65 years with relapsed/refractory FLT3+/− AML (excluding t(8:21) or inv (16)) who are undergoing HLA-matched HSCT are given Sorafenib on D-24 through D-5 with Busulfan/Fludarabine conditioning and then Sorafenib starting between D + 30 and D + 120 for up to 1 year | Primary: MTD and efficacy of Sorafenib when combined with Busulfan/Fludarabine conditioning Secondary: toxicity, neutrophil engraftment, NRM and OS |
|
| Phase II/III Sorafenib for prophylaxis of leukemia relapse in allogeneic HSCT recipients with FLT3-ITD positive AML; n = 196; recruiting | NCT02474290 | Patients 18–60 years with FLT3-ITD + AML who have received alloHSCT will be given Sorafenib vs. control between D + 30 and D + 180 post-transplant | Primary: incidence of relapse Secondary: OS, leukemia-free survival, incidence of toxicity |
|
| Midostaurin | RADIUS Trial (phase II); n = 60; recruiting | NCT01883362 | Patients 18–60 years with FLT3-ITD + AML (excluding M3) who underwent alloHSCT with match related or unrelated donor are randomized to SOC ± Midostaurin for 12 mos in the post-transplant setting | Primary: relapse free survival Secondary: disease free survival, NRM, OS, toxicity, PK of Midostaurin and its metabolites, FLT-ITD mutation status (e.g. mutant:WT) |
| Phase-II study evaluating midostaurin in induction, consolidation and maintenance therapy also after AlloHSCT in patients with newly diagnosed FLT3-ITD + AML; n = 440; recruiting | NCT01477606 | Patients 18–70 years with newly diagnosed FLT3-ITD+ AML (excluding M3, CBFB-MYH11, RUNX1-RUNX1T1 and t(8;21)(q22;q22)) are given Midostaurin during induction, consolidation, and as maintenance (post HSCT or post consolidation) for 1 year | Primary: EFS Secondary: CR rate, relapse free survival, OS, cumulative incidence of relapse, cumulative incidence of death in CR, FLT3 inhibitory activity, QOL, rates of early deaths, death in CR, toxicity, impact of alloHSCT |
|
| Quizartinib | QuANTUM-First trial (Phase III); n = 536; recruiting |
NCT02668653 | Patients 18–75 years with newly diagnosed FLT3-ITD+ AML (excluding M3 and pH+) are randomized to standard induction, consolidation ± HSCT and maintenance chemotherapy with Quizartinib or placebo | Primary: EFS Secondary: OS, CR and composite rate at end of first induction, and % of patients achieving CR with no evidence of MRD |
| QuANTUM-R (Phase III); n = 367; active, not recruiting |
NCT02039726 | Patients ≥18 years with FLT3-ITD+ AML (excluding M3) in first relapse within 6 mos or refractory to prior therapy ± HSCT are randomized to Quizartinib monotherapy or salvage chemotherapy (LoDAC, MEC, or FLAG-IDA) | Primary: OS Secondary: EFS |
|
| Gilteritinib | A Multi-center, randomized, double-blind, placebo-controlled Phase III trial of the FLT3 inhibitor Gilteritinib administered as maintenance therapy following AlloHSCT with FLT3-ITD AML; n = 346; recruiting |
NCT02997202 | Patients ≥ 18years with FLT3-ITD+ AML in CR1 undergoing alloHSCT will be randomized to receive Gilteritinib or placebo between D + 30 and D + 90 after alloHSCT for 2 years. | Primary: relapse-free survival Secondary: toxicity, OS, NRM, EFS at 12 and 24 mos, cumulative incidence of acute GvHD and cumulative incidence of chronic GvHD at 12 and 24 mos, cumulative incidence of detection of FLT3-ITD MRD, incidence of severity of infection |
| Phase 3 open-label, multicenter, randomized study of ASP2215 vs. salvage chemotherapy in patients with relapsed or refractory FLT3-ITD AML; n = 318; recruiting |
NCT03182244 | Patients ≥18 years with relapsed or refractory (including after HSCF) FLT3+ AML (excluding M3 and pH+) are randomized to receive Quizartinib or standard salvage chemotherapy (LoDAC, MEC or FLAG-IDA) | Primary: OS Secondary: EFS, CR, leukemia free survival, duration of CR, CRc, CRi, and CRp, composite CR rate, transplantation rate, brief fatigue inventory, toxicity, effect on laboratory testing (chemistry, hematology, coagulation, urinalysis), vital sign abnormalities, safety assessed by EKG, PK of Quizartinib through max concentration and trough, time after dosing when max concentration occurs, concentration of Quizartinib in blood, effect on ECOG status |
|
| Phase 3 Open-label, Multicenter, Randomized Study of ASP2215 Vs. Salvage Chemotherapy in Patients With Relapsed or Refractory FLT3-ITD AML; n = 369; recruiting |
NCT02421939 | Patients ≥18 years with relapsed or refractory FLT3+ AML (excluding M3 and pH+; including after HSCT) are randomized to receive Quizartinib or standard salvage chemotherapy (LoDAC, Azacitidine, MEC or FLAG-IDA) | Primary: OS and CR and CR with partial hematologic (CRh) rate Secondary: EFS, CR rate, leukemia free survival, duration of remission, CRc rate, transplantation rate, brief fatigue inventory, CRh rate, transfusion conversion rate, transfusion maintenance rate |
|
| Crenolanib | A Phase II Study of Crenolanib Besylate maintenance following AlloHSCT in patients with FLT3+ AML; n = 48; recruiting |
NCT02400255 | Patients ≥18 years with FLT3+ AML who had undergone alloHSCT are split into two cohorts (in CR at time of transplant and not in CR at time of transplant) and given Crenolanib between D + 30 to D + 90 after alloHSCT for up to 728 days | Primary: PFS Secondary: disease free survival, OS, GvHD, 100-day transplant related mortality |
| Dose-finding run-in Phase I followed by a Phase III, multicenter, randomized, double-blind, placebo-controlled study of Crenolanib with chemotherapy in patients with relapsed or refractory FLT3+ AML; n = 276; recruiting | NCT02298166 | Patients ≥18 years with relapsed or refractory (including after HSCT) FLT3+ AML are randomized to standard induction, consolidation and maintenance chemotherapy with Crenolanib or placebo. | Primary: EFS, OS Secondary: CR and CRi rates, cumulative incidence of relapse and death, QOL, rates of early deaths, toxicity |
Abbreviations: Minimal residual disease (MRD); non-relapse mortality (NRM); maximum tolerated dose (MTD); event-free survival (EFS); plasma pharmacokinetics (PK); quality of life (QOL).