Skip to main content

A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML

Trial Status: Active

This study will evaluate the safety, efficacy and pharmacokinetics of midostaurin in combination with standard chemotherapy in pediatrics patients with newly diagnosed FLT3-mutated acute Myeloid Leukemia. the study has two parts : Part 1 to define the Recommended Phase 2 Dose, and the Part 2 to evaluate efficacy and safety of midostaurin. All patients will follow the same treatment regimen consisting in 2 Induction blocks, 3 consolidation blocks, 12 cycles of post-consolidation consisting of continuous therapy with midostaurin, and a follow-up phase.

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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.


Children's Hospital Colorado

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.

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

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CPKC412A2218
  • Secondary IDs NCI-2019-02312, 2017-004830-28
  • ID NCT03591510