Clinical trial

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

ID

Name

CPKC412A2218

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.

Trial arms

Trial start

2019-03-13

Estimated PCD

2025-08-18

Trial end

2029-02-15

Status

Recruiting

Phase

Early phase I

Treatment

Midostaurin

midostaurin 30mg/m2 bid

Arms:

Chemotherapy followed by Midostaurin

Other names:

PKC412

Fludarabine

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

Arms:

Chemotherapy followed by Midostaurin

Other names:

Part 1 Block 2 induction FLADx

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

Arms:

Chemotherapy followed by Midostaurin

Other names:

Part 1:, Block 2 induction FLADx, Block 3 consolidation HAM, Block 4 consolidation HA3E, Block 5 consolidation HIDAC, Part 2:, Block 2 induction HAM, Block 3 consolidation HA3E, Block 4 consolidation HAM

Daunorubicin or idarubicin

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

Arms:

Chemotherapy followed by Midostaurin

Other names:

Part 1 Block 2 induction FLADx

Mitoxantrone

10mg/m2/day D3 and D4

Arms:

Chemotherapy followed by Midostaurin

Other names:

Part 1:, Block 3 consolidation HAM, Part 2:, Block 2 induction HAM, Block 4 consolidation HAM

Etoposide

100mg/m2/day D1 to D5

Arms:

Chemotherapy followed by Midostaurin

Other names:

Part 1:, Block 4 consolidation HA3E, Part 2:, Block 3 consolidation HA3E

Size

23

Primary endpoint

Part 1 of the study: Occurence of dose limiting toxicities (DLT)

From the start of midostaurin treatment in Block 1 to the end of Block 2, from Day 1 to Day 84

Part 2 of the study: To evaluate Safety of midostaurin (30mg/m2 bid or 1 mg/kg bid for participants <10 kg body weight) in sequential combination with chemotherapy followed by 12 cycles of midostaurin post-consolidation therapy.

From the start of treatment up to 5 years follow-up of last patient

Part 2 of the study: To evaluate Tolerability of midostaurin (30mg/m2 bid or 1 mg/kg bid for participants <10 kg body weight) in sequential combination with chemotherapy followed by 12 cycles of midostaurin post-consolidation therapy.

From the start of treatment up to 5 years follow-up of last patient

Eligibility criteria

Inclusion Criteria: * Documented Diagnosis of previously untreated de novo AML according to WHO 2016 criteria * Presence of a FLT3 mutation status as measured/confirmed by a designated lab 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. However, up to 1 week of FLT3 inhibitor (except midostaurin) exposure prior to study enrollment is permissible. Other protocol-defined inclusion/exclusion criteria may apply

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 23, 'type': 'ESTIMATED'}}

Updated at

2024-04-05

1 organization

6 products

1 indication

Organization

Novartis Pharmaceuticals

Product

Indication

Acute Myeloid Leukemia with FLT3 Mutation

Product

Product

Product

Product

Product