Page 20 - 2021_03-Haematologica-web

A. Burchert
Table 2. Trials testing post-hematopoietic stem cell transplantation (HCT) maintenance therapy.
Clinical trial Post-HCT-TKI maintenance therapy only
Patients’ characteristics
- n=60 AML
- only FLT3-ITD+
- age ≥18y and ≤70y
- CHR at inclusion
- first CHR only
- maintenance for 12 months - treatment started 28-60 days
post HCT
- n=83 AML
- only FLT3-ITD
- age ≥18y
- CHR at inclusion
- first or subsequent CHR
- n=202 AML
- only FLT3-ITD
- age ≥18y
- CHR prior to HCT and at
study inclusion
- first or subsequent CHR
- n=346 AML
- only FLT3-ITD
- age ≥18y
- CHR at inclusion - first CHR only
- n=48 AML
- FLT3-ITD and/or TKD D835
mutation
- age ≥18y
- stratified into CHR vs.
no CHR patients
Endpoints
Primary: 18-month RFS
Secondary: OS
Primary: RFS Secondary: OS
Primary: 1-year RFS
Secondary: OS
Primary: RFS Secondary: OS
Primary: PFS Secondary: DFS and OS
Clinical trial register
NCT01883362
DRKS00000591
NCT02474290
Main result
No benefit62
Reduces risk of relapse and death (HR 0.39, P=0.013)63
Reduces risk of relapse and death
1y and 2y RFS: 7% / 12.9% vs. 24.5% / 31.1% (P<0.001)
OS better (P=0.025)64
Results expected 2025
Midostaurin (PKC-412)
Sorafenib
Sorafenib
- phase II (RADIUS)
- randomized
- comparator arm: SOC - open label
Status: completed
- SORMAIN trial
- phase II
- randomized 1:1 - arm A: sorafenib - arm B: placebo - double blind
- treatment starts 60-100 days post HCT - 24 months of therapy
Status: completed
- phase III
- randomized 1:1 - arm A: sorafenib -armB:SOC
- open label
- treatment starts
30-60 days post HCT
- between 120-150 days of
sorafenib (until d+180 post HCT)
Status: completed
MORPHO trial (Astellas Pharma)
- phase III,
- randomized
- arm A (experimental):
gilteritinib
- arm B: placebo
- double blind
- treatment for 24 months
- treatment starts 60-90 days
post HCT
Status: recruiting
- phase II trial (AROG Pharmac Inc.)
- uncontrolled
- CHR or no CHR after HCT - open label
- treatment starts 45-90 days
post HCT Status: recruiting
Gilteritinib
NCT02997202
Crenolanib
NCT02400255
NCT01477606
Results expected 2021
Drug is safe
EFS better than in historical controls
First-line TKI plus chemo-induction/consolidation followed by TKI maintenance (including after HCT)
Midostaurin
- phase II, single arm
- uncontrolled
- chemo/mido combination
first-line; maintenance after chemo (n=22) or HCT (n=75)
- n=284
- FLT3-ITD+
- age ≥18y and ≤70y
- maintenance for 12 months
- treatment started 30-100 days
post HCT
Primary: EFS
2. OS
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