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: Apr 28, 2022

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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
Novartis Investigative Site
Recruiting
Wien, A 1090
-
Austria
Czech Republic
Novartis Investigative Site
Recruiting
Brno, 613 00
-
Czech Republic
Novartis Investigative Site
Recruiting
Praha 5, 150 06
-
Czech Republic
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Italy
Novartis Investigative Site
Recruiting
Bologna, 40138
BO
Italy
Novartis Investigative Site
Recruiting
Genova, 16147
GE
Italy
Novartis Investigative Site
Recruiting
Monza, 20900
MB
Italy
Novartis Investigative Site
Recruiting
Roma, 00165
RM
Italy
Novartis Investigative Site
Recruiting
Napoli, 80100
-
Italy
Japan
Novartis Investigative Site
Recruiting
Kobe-city, 650-0047
Hyogo
Japan
Novartis Investigative Site
Recruiting
Saitama, 330 8777
-
Japan
Novartis Investigative Site
Recruiting
Shizuoka, 420 8660
-
Japan
Jordan
Novartis Investigative Site
Recruiting
Amman, 11941
-
Jordan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
-
Korea, Republic of
Poland
Novartis Investigative Site
Recruiting
Gdansk, 80 952
-
Poland
Novartis Investigative Site
Recruiting
Krakow,
-
Poland
Russian Federation
Novartis Investigative Site
Recruiting
Ekaterinburg, 620149
-
Russian Federation
Slovenia
Novartis Investigative Site
Recruiting
Ljubljana, 1000
-
Slovenia
Turkey
Novartis Investigative Site
Recruiting
Adana, 1330
-
Turkey
Novartis Investigative Site
Recruiting
Antalya, 07070
-
Turkey

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

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Call 1-888-669-6682 or email [email protected]