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

  • STATUS
    Recruiting
  • End date
    Feb 15, 2029
  • participants needed
    50
  • sponsor
    Novartis Pharmaceuticals
Updated on 4 July 2021
Investigator
Novartis Pharmaceuticals
Primary Contact
Novartis Investigative Site (7.5 mi away) Contact
+18 other location

Summary

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 Part 2 to evaluate safety and tolerability and efficacy of midostaurin. Both parts will consist of 2 induction blocks, 3 consolidation blocks, 12 cycles of post-consolidation consisting of continuous therapy with midostaurin, and a follow-up phase.

Description

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 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.
  • 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 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. Patienta who achieve 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.
  • 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. Patient in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin, during 12 cycles (28 days per cycle).

Details
Condition FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia, FLT3-mutated Acute Myeloid Leukemia
Treatment cytarabine, etoposide, Fludarabine, Mitoxantrone, Midostaurin, Daunorubicin liposomal or daunorubicin or idarubicin, Daunorubicin or idarubicin
Clinical Study IdentifierNCT03591510
SponsorNovartis Pharmaceuticals
Last Modified on4 July 2021

Eligibility

Yes No Not Sure

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
Other protocol-defined inclusion/exclusion criteria may apply
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