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

A Phase II, Open-label, Single Arm Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Twice Daily Midostaurin (PKC412) Combined With Standard Chemotherapy and as a Single Agent Post-consolidation Therapy in Children With Untreated FLT3-mutated AML

ClinicalTrials.gov Identifier: NCT03591510

Novartis Reference Number: CPKC412A2218

Last Update: Jan 23, 2023

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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.

Condition

FLT3-mutated Acute Myeloid Leukemia

Phase

Phase 2

Overall status

Recruiting

Start date

Mar 13, 2019

Completion date

Feb 15, 2029

Gender

All

Age(s)

3 Years - 17 Years (Child)

Interventions

Drug

Midostaurin

midostaurin 30mg/m2 bid

Drug

Fludarabine

30mg/m2/day on D1-D5 of Block 2 FLADx

Drug

Cytarabine

Part 1: 2000mg/m2/day D1 to D5 of Block 2 FLADx 1000mg/m2 every 12 hours D1 to D3 Block 3 HAM 3000mg/m2 every 12 hours D1 to D3 Block 4 HA3E 3000mg/m2 every 12 hours D1 to D3 Block 5 HIDAC Part 2: 1000mg/m2 every 12 hours D1 to D3 Block 2 HAM 3000mg/m2 every 12 hours D1 to D3 Block 3 HA3E 1000mg/m2 every 12 hours D1 to D3 Block 4 HAM 3000mg/m2 every 12 hours D1 to D3 Block 5 HIDAC

Drug

Daunorubicin or idarubicin

daunorubicin 60 mg/m2/day OR idarubicin 12mg/m2/day On D2, D4, D6 of Block 2 FLADx

Drug

Mitoxantrone

10mg/m2/day D3 and D4

Drug

Etoposide

100mg/m2/day D1 to D5

Eligibility Criteria

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

Study Locations

United States

Miami Children s Hospital

Recruiting

Miami, 33155 - Florida

Contact: Jose Rodriguez-Alonso (305-668-5576) - [email protected] - Guillermo DeAngulo

United States

Austria