Table 2.
Selected Clinical Trials of Approved FLT3i in Different Therapeutic Settings
| Phase- Clinical Trial Number | Therapeutic Approach Including FLT3i | Patient Group | Response | Status |
|---|---|---|---|---|
| Phase III NCT02752035 | Gilteritinib + Azacitidine | Newly diagnosed AML with FLT3 mutation and not eligible for induction chemotherapy | No significant OS with improved CR rates | Active, not recruiting |
| Phase II NCT01253070 | Sorafenib + chemotherapy (daunorubicin hydrochloride and cytarabine) | AML patients (≥60 years of age) with FLT3-ITD or -TKD mutations and have not received chemotherapy |
CR after induction therapy FLT3-ITD: 74% FLT3-TKD: 73% 1-year OS FLT3-ITD: 62% FLT3-TKD: 71% 1-year DFS FLT3-ITD: 52% FLT3-TKD:36% 1-year EFS FLT3-ITD: 39% FLT3-TKD: 27% |
Active, not recruiting |
| Phase I/II NCT01892371 | Quizartinib + Azacitidine or Cytarabine | Refractory or relapsed MDS, CMML or AML patients with or without FLT3 mutation |
CRc 64% with azacitidine 29% with low-dose cytarabine RFS 5.8 with azacitidine and 6.2 months with low-dose cytarabine OS 12.8 with azacitidine and 4 months with low-dose cytarabine |
Active, not recruiting |
| Phase III NCT04174612 | Midostaurin + Daunorubicin + Cytarabine | Newly diagnosed AML patients with FLT3 mutation between the age of 18 and 65 | No results posted | Recruiting |
| Phase III NCT03182244 | Gilteritinib vs salvage chemotherapy | Patients with relapsed or refractory AML with FLT3 mutation after first line therapy | No results posted | Active, not recruiting |
| Phase I NCT05024552 | Gilteritinib + Vyxeos (cytarabine/ daunorubicin liposomal complex) | Patients with relapsed or refractory AML with FLT3 mutation | No results posted | Recruiting |
| Phase II NCT03135054 | Quizartinib + Omacetaxine Mepesuccinate (Homoharringtonine) Injection | Newly diagnosed or relapsed/refractory AML patients with FLT3-ITD mutation | No results posted | Active, not recruiting |
| Phase II NCT03170895 | Sorafenib + Omacetaxine Mepesuccinate Injection | Newly diagnosed or relapsed/refractory AML patients with FLT3-ITD mutation |
CR/CRi rate for R/R patients: 72% LFS and OS: 5.6 and 10.9 months |
Completed |
| Phase II NCT03622541 | Sorafenib | Relapsed or refractory AML patients with FLT3-ITD mutation | No results posted | Completed |
| Phase I/II NCT03730012 | Gilteritinib + Atezolizumab (PD-L1 mAb) | Relapsed or refractory AML patients with FLT3 mutation |
CRc Gilteritinib 120 mg + Atezolizumab 420 mg: 33.3% Gilteritinib 120 mg + Atezolizumab 840 mg:12.5% CR Gilteritinib 120 mg + Atezolizumab 420 mg:33.3% Gilteritinib 120 mg + Atezolizumab 840 mg: 0% |
Completed |
| Phase I/II NCT04240002 | Gilteritinib + Fludarabine + Cytarabine + G-CSF | Children and young adults with relapsed or refractory FLT3-ITD+ AML | No results posted | Recruiting |
| Phase II NCT02927262 | Gilteritinib | Patients with FLT3-ITD or FLT3-TKD mutated AML |
RFS up to 2 years - 24.02 months EFS up to 2 years - 16.06 months |
Active, not recruiting |
| Phase I NCT00943943 | G-CSF + Plerixafor (CXCR4 inhibitor) + Sorafenib | Relapsed or refractory AML patients with FLT3 mutation | Response rate 36% | Completed |
| Phase III NCT02421939 | Gilteritinib | Relapsed or refractory AML patients with FLT3 mutation |
CR Gilteritinib: 21.1% Salvage Chemotherapy: 10.5% CR/CRh Gilteritinib: 34% Salvage Chemotherapy: 15.3% OS (months) Gilteritinib: 9.3 Salvage Chemotherapy: 5.6 EFS (months) Gilteritinib:2.8 Salvage Chemotherapy: 0.7 |
Active, not recruiting |
| Phase II NCT02196857 | Azacitidine + Sorafenib | AML and high risk MDS patients with FLT3-ITD mutation |
CR: 26% OS: 8.3 months RFS: 7.1 months |
Completed |
| Phase III NCT04027309 | Gilteritinib or midostaurin | AML or MDS patients with excess of blasts-2 and FLT3 mutation | No results posted | Recruiting |
| Phase II NCT02984995 | Quizartinib | Relapsed or refractory AML patients with FLT3-ITD mutation |
CRc 20mg/Day Quizartinib: 33.3% 30mg/Day Quizartinib: 56.5% OS (weeks) 20mg/Day Quizartinib: NA 30mg/Day Quizartinib: 34.1 EFS (weeks) 20mg/Day Quizartinib: 0.1 30mg/Day Quizartinib: 12.7 LFS (weeks) 20mg/Day Quizartinib: NA 30mg/Day Quizartinib: 16.1 |
Completed |
| Phase I/II NCT05010122 | Decitabine and Cedazuridine + Gilteritinib + Venetoclax | Newly diagnosed, relapsed or refractory AML or high risk MDS patients with FLT3 mutation | No results posted | Recruiting |
| Phase I/II NCT04140487 | Azacitidine + Gilteritinib + Venetoclax | Relapsed or refractory AML, CMML or MDS/MPN patients with FLT3 mutation | No results posted | Recruiting |
| Phase I/II NCT03793478 | Quizartinib + Intrathecal (IT) triple chemotherapy prophylaxis + Fludarabine + Cytarabine + Etoposide | Relapsed or refractory AML patients (1 month to 25 years of age) with FLT3-ITD mutation | No results posted | Recruiting |
| Phase III NCT02997202 | Gilteritinib | AML patients with FLT3-ITD mutation in CR1 | No results posted | Active, not recruiting |
| Phase II NCT03836209 | Daunorubicin + Cytarabine + Gilteritinib or Midostaurin | AML patients with FLT3 mutation | No results posted | Recruiting |
| Phase III NCT02039726 | Quizartinib | AML patients with FLT3-ITD mutation |
OS (months) Quizartinib: 6.2 Salvage Chemotherapy: 4.7 EFS (months) Quizartinib: 1.4 Salvage Chemotherapy: 0.9 months |
Completed |
| Phase I/II NCT04687761 | Quizartinib + Venetoclax + Azacitidine or Cytarabine | Newly diagnosed AML patients (≥60 years of age) | No results posted | Recruiting |
| Phase I/II NCT03661307 | Quizartinib + Decitabine + Venetoclax | Untreated or relapsed AML patients or high risk MDS | No results posted | Recruiting |
| Phase I NCT04496999 | Midostaurin + HDM201 (MDM2 inhibitor) | Relapsed or refractory AML patients with FLT3 mutation and WT-TP53 | No results posted | Recruiting |
| Phase I/II NCT04385290 | Midostaurin + Daunorubicin + Cytarabine+ Gemtuzumab Ozogamicin | Newly diagnosed AML patients | No results posted | Active, not recruiting |
| Phase I/II NCT01254890 | Azacitidin + Sorafenib | Refractory AML, CMML or MDS patients and relapsed AML patients |
CR: 16% OS: 6.2 months EFS: 3.8 months |
Completed |
| Phase III NCT00651261 | Midostaurin + Cytarabine + Daunorubicin + Dexamethasone Acetate | Newly diagnosed AML patients with FLT3 mutation |
OS (months) Midostaurin: 74.7 Placebo: 25.6 CR Midostaurin: 58.9% Placebo: 53.5% EFS (months) Midostaurin: 8.2 Placebo: 3.0 |
Active, not recruiting |
Abbreviations: CR, complete remission; CRc, composite complete remission; CR/CRh, complete remission and complete remission with partial hematological recovery; OS, overall survival; DFS, disease-free survival; EFS, event-free survival; RFS, relapse-free survival; LFS, leukemia-free survival; G-CSF, granulocyte colony-stimulating factor.