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

NCT ID: NCT03591510

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-13

Study Completion Date

2029-09-02

Brief Summary

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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.

Detailed Description

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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 documented CR (and 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. Patients who relapse will discontinue further study treatment.
* 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 who relapse will discontinue further study treatment.

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. Patients who achieve documented CR (and 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. Patients who relapse will discontinue further study treatment.
* 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. Patients who relapse will discontinue further study treatment.

Patients in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin, during 12 cycles (28 days per cycle). Patients who relapse will discontinue further study treatment.

Conditions

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FLT3-mutated Acute Myeloid Leukemia

Keywords

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PKC412 Acute Myeloid Leukemia AML FLT3-mutated pediatric population midostaurin midostaurin combined with standard chemotherapy single agent post-consolidation therapy untreated FLT3-mutated AML

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy followed by Midostaurin

In Part 1, midostaurin with standard induction (Block 1 induction according to local practice, Block 2 induction containing fludarabine, cytarabine, daunorubicin/idarubicin) and consolidation (Block 3: cytarabine + mitoxantrone, Block 4: cytarabine + etoposide, Block 5: cytarabine) followed by single agent midostaurin post-consolidation therapy.

In Part 2, midostaurin with standard induction (Block 1 induction according to local practice, Block 2 induction containing cytarabine + mitoxantrone) and consolidation (Block 3: cytarabine + etoposide, Block 4: cytarabine + mitoxantrone, Block 5: cytarabine) followed by single agent midostaurin post-consolidation therapy.

Group Type EXPERIMENTAL

Midostaurin

Intervention Type DRUG

midostaurin 30mg/m2 bid

Fludarabine

Intervention Type DRUG

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

Cytarabine

Intervention Type DRUG

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

Daunorubicin or idarubicin

Intervention Type DRUG

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

Mitoxantrone

Intervention Type DRUG

10mg/m2/day D3 and D4

Etoposide

Intervention Type DRUG

100mg/m2/day D1 to D5

Interventions

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Midostaurin

midostaurin 30mg/m2 bid

Intervention Type DRUG

Fludarabine

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

Intervention Type 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

Intervention Type DRUG

Daunorubicin or idarubicin

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

Intervention Type DRUG

Mitoxantrone

10mg/m2/day D3 and D4

Intervention Type DRUG

Etoposide

100mg/m2/day D1 to D5

Intervention Type DRUG

Other Intervention Names

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PKC412 Part 1 Block 2 induction FLADx 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 Part 1 Block 2 induction FLADx Part 1: Block 3 consolidation HAM Part 2: Block 2 induction HAM Block 4 consolidation HAM Part 1: Block 4 consolidation HA3E Part 2: Block 3 consolidation HA3E

Eligibility Criteria

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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.
Minimum Eligible Age

3 Months

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Prague, , Czechia

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Pavia, PV, Italy

Site Status

Novartis Investigative Site

Roma, RM, Italy

Site Status

Novartis Investigative Site

Torino, TO, Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Osaka, , Japan

Site Status

Novartis Investigative Site

Amman, , Jordan

Site Status

Novartis Investigative Site

Krakow, , Poland

Site Status

Novartis Investigative Site

Moscow, , Russia

Site Status

Novartis Investigative Site

Ljubljana, , Slovenia

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Adana, Adana, Turkey (Türkiye)

Site Status

Countries

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Austria Greece United States Czechia Germany Italy Japan Jordan Poland Russia Slovenia South Korea Turkey (Türkiye)

Other Identifiers

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2017-004830-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPKC412A2218

Identifier Type: -

Identifier Source: org_study_id