This trial is an open label, multi center single arm study to evaluate twice daily oral
midostaurin with standard induction, consolidation chemotherapy with sequential
midostaurin therapy for 5 treatment blocks (2 induction blocks, 3 consolidation blocks,
followed by single agent midostaurin post consolidation therapy for 12 cycles).
The total maximum planned duration on treatment is 17 cycles (5 blocks and 12 cycles). A
block is defined as the time from start of study treatment to the time of hematopoietic
recovery, at the latest at Day (D) 42, or determination of persistent disease, whichever
occur first.
In both Part 1 and Part 2, patients will receive the first course of induction
chemotherapy according to local standard and duration is from 8 to 12 days. Upon FLT3
mutation confirmation, patients will receive midostaurin for 14 days. After determination
of remission and hematopoietic recovery, patients will receive Block 2.
In Part 1:
- Block 2 FLADx treatment duration is D1 to D6, and midostaurin from D8 to D21.
Patients who achieve documented CR (and hematopoietic recovery at the latest at D42
from the first day of Block 2) will receive Block 3.
- Block 3 consolidation HAM treatment duration is D1 to D4, followed by midostaurin D8
to D21. Patients who achieve hematopoietic recovery at the latest at D42 from the
first day of Block 3 will receive Block 4. Patients who relapse will discontinue
further study treatment.
- Block 4 HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21.
Patients who achieve hematopoietic recovery at the latest at D42 from the first day
of Block 4 will receive Block 5.
- Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21.
Patients who relapse will discontinue further study treatment.
Patients in continuous remission with hematopoietic recovery will receive continuous post
consolidation therapy of midostaurin, during 12 cycles (28 days per cycle).
In Part 1 of the study, patients in cohorts of 3 will receive sequential midostaurin
administered at 30mg/m2bid. If the 30mg/m2 bid is well tolerated as measured by the Dose
Limited Toxicity (DLT) rate during Bock 1, additional patients in cohort of 3 will be
treated with sequential midostaurin at 60mg/m2 bid. When the recommended phase 2 dose
(RP2D) is confirmed, subsequent patients will be treated in Part 2 of the study at the
RP2D.
In Part 2:
- Block 2 HAM treatment duration is D1 to D4 and midostaurin from D8 to D21. Patients
who achieve documented CR (and hematopoietic recovery at the latest at D42 from the
first day of Block 2) will receive Block 3.
- Block 3 consolidation HA3E treatment duration is D1 to D5, followed by midostaurin
D8 to D21. Patients who achieve hematopoietic recovery at the latest at D42 from the
first day of Block 3 will receive Block 4. Patients who relapse will discontinue
further study treatment.
- Block 4 HAM treatment duration is D1 to D4 followed by midostaurin D8 to D21.
Patients who achieve hematopoietic recovery at the latest at D42 from the first day
of Block 4 will receive Block 5.
- Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21.
Patients who relapse will discontinue further study treatment.
Patients in continuous remission with hematopoietic recovery will receive continuous post
consolidation therapy of midostaurin, during 12 cycles (28 days per cycle). Patients who
relapse will discontinue further study treatment.
