FLT3-mutated Acute Myeloid LeukemiaPhase 2NCT03591510
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 2 study testing Midostaurin, Fludarabine and Cytarabine in people with FLT3-mutated Acute Myeloid Leukemia, run by Novartis Pharmaceuticals at 15 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- FLT3-mutated Acute Myeloid Leukemia
- What is being tested?
- Midostaurin, Fludarabine and Cytarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 15 sitesin 10 countries
- Study dates
- 13 Mar 2019to 18 May 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
15 sites in 10 countries.
15 sites in 10 countries
Italy4 sites
Novartis Investigative Site
Naples, 80122
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Roma, RM, 00165
Novartis Investigative Site
Torino, TO, 10126
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Essen, 45147
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 05505
Turkey (Türkiye)1 site
Novartis Investigative Site
Adana, Adana, 1330
About this study
Official title: 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
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.
Read the detailed description
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
- FLT3-mutated Acute Myeloid Leukemia
- Being tested
- Midostaurin, Fludarabine, Cytarabine, Daunorubicin or idarubicin, Mitoxantrone
- Keywords
- PKC412, Acute Myeloid Leukemia, AML, FLT3-mutated, pediatric population, midostaurin, midostaurin combined with standard chemotherapy, single agent post-consolidation therapy, untreated FLT3-mutated AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidostaurinDrug
Also called PKC412
midostaurin 30mg/m2 bid
FludarabineDrug
Also called Part 1 Block 2 induction FLADx
30mg/m2/day on D1-D5 of Block 2 FLADx
CytarabineDrug
Also called Part 1:, Block 2 induction FLADx, Block 3 consolidation HAM, Block 4 consolidation HA3E
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 idarubicinDrug
Also called Part 1 Block 2 induction FLADx
daunorubicin 60 mg/m2/day OR idarubicin 12mg/m2/day On D2, D4, D6 of Block 2 FLADx
MitoxantroneDrug
Also called Part 1:, Block 3 consolidation HAM, Part 2:, Block 2 induction HAM
10mg/m2/day D3 and D4
EtoposideDrug
Also called Part 1:, Block 4 consolidation HA3E, Part 2:, Block 3 consolidation HA3E
100mg/m2/day D1 to D5
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Midostaurin; Drug: Fludarabine; Drug: Cytarabine; Drug: Daunorubicin or idarubicin; Drug: Mitoxantrone; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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)
Percentage of participants with a response of CR, CRi or modified CRi at the end of Block 2
Measured: 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
TTR is defined as the time between start of treatment to the date of first onset of response (CR, CRi or modified CRi).
Response duration is defined as the time from CR, CRi or modified CRi to relapse or death due to any cause.
Measured: From the start of treatment up to 5 years follow-up of last patient
Part 2 of the study: Event Free Survival (EFS)
EFS is defined as the time from Day 1 of chemotherapy until an EFS event is observed.
An EFS event is defined as a failure to obtain CR/Modified CRi within induction, relapse after CR/modified CRi, or death due to any cause, whichever occurs first. EFS will be measured after all participants completed at least 18 months of follow-up.
Measured: 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)
OS is defined as the time from Day 1 of chemotherapy to the date of death due to any cause.
Measured: 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)
DFS is defined as the time from CR/modified CRi in induction to relapse or death due to any cause
Measured: From the start of treatment up to 5 years follow-up of last patient
Part 2 of the study: Percentage of participants with MRD negative status during each study phase
Percentage of patient with MRD negative status by multiparameter flow cytometry
Measured: MRD is evaluated at Day 14 after end of chemotherapy induction Block 1, at Day 21 of Blocks 2, 3, 4 and 5, and Cycle 7 during post-consolidation phase (each block could last up to 42 days)
Part 2 of the study: Palatability of oral solution of midostaurin
Palatability is assessed through questionnaires- Palatability PRO and obsPRO
Measured: Day 14 after end of chemotherapy induction Block 1, Day 21 of Blocks 2, 3, 4 and 5 (each block can last up to 42 days), post-consolidation Cycle 1, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11
Part 2 of the study: Percentage of blasts in bone marrow and peripheral blood
Bone marrow and peripheral blood parameters and extramedullar involvement at the end of induction Block 1 and Block 2
Measured: Parameters are assessed 14 days after end of chemotherapy induction Block 1 and Day 14 induction Block 2
Part 1 and Part 2 of the study: Plasma concentrations of midostaurin and its metabolites
Plasma concentration of midostaurin and its 2 metabolites
Measured: Days 1, 7 & 14 after end of local chemotherapy-induction in Block 1, Days 14 & 21 of Block 2, Day 21 of Blocks 3, 4 & 5 (each block can last up to 42 days), in-post consolidation Day 1 of Cycle (C)2, C3, C5, C7, C9 and C12 (each cycle = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2018
- Study start13 Mar 2019
- Primary completion18 May 2029 (estimated)
- Study completion18 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FLT3-mutated Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03591510
- Sponsor's protocol ID
- CPKC412A2218
- Other IDs
- 2017-004830-28, 2017
- Status last verified
- Jul 2026
- First submitted
- 25 Jun 2018
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 ID
- NCT03591510
- Acronym / sponsor ID
- CPKC412A2218
- Conditions
- FLT3-mutated Acute Myeloid Leukemia
- Keywords
- PKC412, Acute Myeloid Leukemia, AML, FLT3-mutated, pediatric population, midostaurin, midostaurin combined with standard chemotherapy, single agent post-consolidation therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2019 (actual)
- Primary completion
- 18 May 2029 (estimated)
- Study completion
- 18 May 2029 (estimated)
- First posted
- 19 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy followed by Midostaurin | Experimental | Drug: Midostaurin, Drug: Fludarabine, Drug: Cytarabine, Drug: Daunorubicin or idarubicin, Drug: Mitoxantrone, Drug: EtoposideIn 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. |
Who may qualify
- Ages
- 3 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MidostaurinAlso: PKC412midostaurin 30mg/m2 bid | Drug | Chemotherapy followed by Midostaurin |
| FludarabineAlso: Part 1 Block 2 induction FLADx30mg/m2/day on D1-D5 of Block 2 FLADx | Drug | Chemotherapy followed by Midostaurin |
| CytarabineAlso: Part 1:, Block 2 induction FLADx, Block 3 consolidation HAM, Block 4 consolidation HA3EPart 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 | Chemotherapy followed by Midostaurin |
| Daunorubicin or idarubicinAlso: Part 1 Block 2 induction FLADxdaunorubicin 60 mg/m2/day OR idarubicin 12mg/m2/day On D2, D4, D6 of Block 2 FLADx | Drug | Chemotherapy followed by Midostaurin |
| MitoxantroneAlso: Part 1:, Block 3 consolidation HAM, Part 2:, Block 2 induction HAM10mg/m2/day D3 and D4 | Drug | Chemotherapy followed by Midostaurin |
| EtoposideAlso: Part 1:, Block 4 consolidation HA3E, Part 2:, Block 3 consolidation HA3E100mg/m2/day D1 to D5 | Drug | Chemotherapy followed by Midostaurin |
Primary outcome
Part 1 of the study: Occurence of dose limiting toxicities (DLT)
Time frame: From the start of midostaurin treatment in Block 1 to the end of Block 2, from Day 1 to Day 84
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.
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.
Time frame: From the start of treatment up to 5 years follow-up of last patient
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
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.
Time frame: From the start of treatment up to 5 years follow-up of last patient
Number of dose interruptions/reductions and discontinuations due to study drug
9 secondary outcomes
Part 2 of the study: Percentage of participants with response (CR, CR/modified CRi and CR/CRi)
Time frame: 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
Time frame: From the start of treatment up to 5 years follow-up of last patient
Part 2 of the study: Event Free Survival (EFS)
Time frame: 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)
Time frame: 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)
Time frame: From the start of treatment up to 5 years follow-up of last patient
Part 2 of the study: Percentage of participants with MRD negative status during each study phase
Time frame: MRD is evaluated at Day 14 after end of chemotherapy induction Block 1, at Day 21 of Blocks 2, 3, 4 and 5, and Cycle 7 during post-consolidation phase (each block could last up to 42 days)
Part 2 of the study: Palatability of oral solution of midostaurin
Time frame: Day 14 after end of chemotherapy induction Block 1, Day 21 of Blocks 2, 3, 4 and 5 (each block can last up to 42 days), post-consolidation Cycle 1, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11
Part 2 of the study: Percentage of blasts in bone marrow and peripheral blood
Time frame: Parameters are assessed 14 days after end of chemotherapy induction Block 1 and Day 14 induction Block 2
Part 1 and Part 2 of the study: Plasma concentrations of midostaurin and its metabolites
Time frame: Days 1, 7 & 14 after end of local chemotherapy-induction in Block 1, Days 14 & 21 of Block 2, Day 21 of Blocks 3, 4 & 5 (each block can last up to 42 days), in-post consolidation Day 1 of Cycle (C)2, C3, C5, C7, C9 and C12 (each cycle = 28 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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Recurrent Acute Myeloid Leukemia, Recurrent Chronic Myelomonocytic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midostaurin, Fludarabine and Cytarabine in people with FLT3-mutated Acute Myeloid Leukemia, run by Novartis Pharmaceuticals at 15 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Italy, Germany, South Korea, Czechia, Japan and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 of the study: Occurence of dose limiting toxicities (DLT) (time frame: From the start of midostaurin treatment in Block 1 to the end of Block 2, from Day 1 to Day 84). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.