NCT03591510|Active Not RecruitingPhase 2DMCFDA Drug

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

Novartis Pharmaceuticals ClinicalTrials.gov

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2 other identifiers

CPKC412A22182017-004830-28

Study Type

interventional

Target

Locations

10 countries

Sites

Timeline

RegisteredJul 2018

StartedMar 2019

CompletionMay 2029

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

37mo left

Started Mar 2019

Longer than P75 for phase_2

Geographic Reach

10 countries

15 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

10.2 years study duration

Study Progress70%

Mar 2019May 2029

First Submitted

Initial submission to the registry

June 25, 2018

Completed

24 days until next milestone

First Posted

Study publicly available on registry

July 19, 2018

Completed

8 months until next milestone

Study Start

First participant enrolled

March 13, 2019

Completed

6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 19, 2026

Completed

3.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2029

Expected

Last Updated

April 27, 2026

Status Verified

April 1, 2026

Enrollment Period

6.9 years

First QC Date

June 25, 2018

Last Update Submit

April 23, 2026

Conditions

FLT3-mutated Acute Myeloid Leukemia

Keywords

PKC412Acute Myeloid LeukemiaAMLFLT3-mutatedpediatric populationmidostaurinmidostaurin combined with standard chemotherapysingle agent post-consolidation therapyuntreated FLT3-mutated AML

Outcome Measures

Primary Outcomes (3)

Part 1 of the study: Occurence of dose limiting toxicities (DLT)
Dose-limiting toxicity (DLT) is defined as any death due to toxicity related to study treatment (chemotherapy + midostaurin) and/or any CTCAE grade 4 non-hematological adverse event or abnormal laboratory value grade 4 related to study treatment unless the event improves sufficiently by day 42 and therefore does not further delay the next cycle of study treatment.
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.
Safety profile includes type, frequency and severity of adverse events during the induction, consolidation and post consolidation phase. AEs are also collected during post treatment follow-up phase
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.
Number of dose interruptions/reductions and discontinuations due to study drug
From the start of treatment up to 5 years follow-up of last patient

Secondary Outcomes (9)

Part 2 of the study: Percentage of participants with response (CR, CR/modified CRi and CR/CRi)
From the start of treatment in Block 1 to the end of Block 2, from Day 1 up to Day 84
Part 2 of the study: Time to response (TTR) and response duration
From the start of treatment up to 5 years follow-up of last patient
Part 2 of the study: Event Free Survival (EFS)
From the start of treatment to time when all patients have completed at least 18 months of follow up (~ 48 months)
Part 2 of the study: Overall Survival (OS)
At each visit, every 3 months after last follow-up visit and up to 5 years after last patient first treatment
Part 2 of the study: Disease free survival (DFS)
From the start of treatment up to 5 years follow-up of last patient
+4 more secondary outcomes

Study Arms (1)

Chemotherapy followed by Midostaurin

EXPERIMENTAL

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.

Drug: MidostaurinDrug: FludarabineDrug: CytarabineDrug: Daunorubicin or idarubicinDrug: MitoxantroneDrug: Etoposide