A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML
- Documented Diagnosis of previously untreated de novo AML according to WHO 2016 criteria
- Presence of a FLT3 mutation status with results available prior first dose of Midostaurin
- Patients with Lansky or Karnofsky performance status equal or superior to 60
- Patient with the following laboratory value : AST and ALT ≤ 3times ULN
- Serum Total bilirubin ≤ 1.5times ULN
- Estimated creatinine clearance ≥30ml/min
- Any concurrent malignancy, AML with philadelphia Chromosome, AML-DS, JMML
- Symptomatic leukemic CNS involvement
- isolated extramedullary leukemia, secondary AML and MDS
- Acute Promyelocytic Leukemia with the PML RARA rearrangement
- patient who have received prior treatment with a FLT3 inhibitor.
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, which occur
patient will receive the firs course of induction chemotherapy according to local standard
and duration is from 8 to 12 days. Upon FLT3 mutation is confirmed, patient will receive
midostaurin for 14 days. After determination of remission and hematopoietic recovery, patient
will receive Block 2.
Block 2 FLADx treatment duration is D1 to D6, and midostaurin from D8 to D21. patient who
achieve hematopoietic recovery at the latest at D42 from the first day of block 2 will
receive block 3.
Block3 consolidation HAM treatment duration is D1 to D4, followed by midostaurin D8 to D21
.patient who achieve hematopoietic recovery at the latest at D42 from the first day of block
3 will receive block 4.
Block 4 HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21. Patient who
achieve hematopoietic recovery at the latest at D42 from the first day of block 4will receive
Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21. Patient 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 cohort 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 block 1, additional patients in cohort of 3 will be
treated with sequential midostaurin at 60mg/m2 bid.
when the recommended 2 dose (RP2D) is confirmed, subsequent patients will be treated in the
part 2 of the study at the RP2D.
Trial Phase Phase II
Trial Type Treatment
Novartis Pharmaceuticals Corporation
- Primary ID CPKC412A2218
- Secondary IDs NCI-2019-02312, 2017-004830-28
- Clinicaltrials.gov ID NCT03591510