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All Conditions

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Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Amino Acids

Etoposide

Cytarabine

Mitoxantrone

Fludarabine

Fludarabine phosphate

Azacitidine

Lenograstim

Etoposide phosphate

Gilteritinib

Idarubicin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Antiviral Agents

Adjuvants, Immunologic

Anti-Bacterial Agents

Antibiotics, Antitubercular

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.

Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m\^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m\^2 daily by IV for 5 days, etoposide 100 mg/m\^2 daily by IV for 5 days and cytarabine 1000 mg/m\^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m\^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m\^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m\^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m\^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.

gilteritinib

subcutaneous (SC) or intravenous (IV) injection

LoDAC (Low Dose Cytarabine)

MEC (Mitoxantrone, Etoposide, Cytarabine)

SC (G-CSF) and IV (Fludarabine, Cytarabine, Idarubicin) injection

FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin)

Executive Medical Director

The purpose of this study is to determine the clinical benefit of ASP2215 therapy in participants with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia (AML) who are refractory to or have relapsed after first-line AML therapy as shown with overall survival (OS) compared to salvage chemotherapy, and to determine the efficacy of ASP2215 therapy as assessed by the rate of complete remission and complete remission with partial hematological recovery (CR/CRh) in these participants.

This study will also determine the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.

Participants considered an adult according to local regulations at the time of signing informed consent may participate in this study. Participants will be randomized in a 2:1 ratio to receive ASP2215 or salvage chemotherapy. Participants will enter the screening period up to 14 days prior to the start of treatment. Prior to randomization, a salvage chemotherapy regimen will be pre-selected for each participant; options will include low-dose cytarabine (LoDAC), azacitidine, mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC), or fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) with idarubicin (FLAG-IDA). The randomization will be stratified by response to first-line therapy and pre-selected salvage chemotherapy. Participants will be administered treatment over continuous 28-day cycles.

After treatment discontinuation, participants will have a pre-hematopoietic stem cell transplant (HSCT)/end-of-treatment visit within 7 days after treatment discontinuation, followed by a 30-day follow-up for safety, in which a telephone contact with the participant is sufficient unless any assessment must be repeated for resolution of treatment-related adverse events (AEs). After that, long term follow-up will be done every 3 months up to 3 years from the participant's end-of-treatment visit.

A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation

A Phase 3 Open-Label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Overall survival was defined as the time from the date of randomization until the date of death from any cause (death date - randomization date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - randomized date + 1). The date of last contact was the latest date that the participant was known to be alive by the cutoff date. The last contact date was derived for participants alive at the analysis cutoff date. Survival rate and 95% CI were estimated using the Kaplan-Meier method and the Greenwood formula.

The CR/CRh rate was defined as the number of participants who achieved either CR or CRh at any of the postbaseline visits divided by the number of participants in the analysis population.

EFS was defined as the time from the date of randomization until the date of documented relapse (excluding relapse after PR), treatment failure or death from any cause within 30 days after the last dose of study drug, whichever occurred first (earliest of \[relapse date, treatment failure date, death date\] - randomization date + 1). If a participant experienced relapse or death within 30 days after the last dose of study drug, the participant was defined as having an EFS event related to either "relapse" or "death", and the event date was the date of relapse or death. For a participant who was not known to have had a relapse or treatment failure or death event, EFS was censored at the date of last relapse-free disease assessment (last relapse-free disease assessment date - randomization date + 1). Data was estimated based on Kaplan-Meier estimates.

The CR rate was defined as the number of participants who achieved the best response of CR divided by the number of participants in the analysis population.

The LFS was defined as the time from the date of first CRc until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CRc (relapse date or death date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1).

Duration of remission included duration of composite complete remission (CRc), duration of complete remission (CR)/ complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR and duration of response (CRc + partial remission (PR). The duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse (i.e., the date of first NR after CRc or PR) for participants who achieved CRc or PR (relapse date - first CRc or PR disease assessment date + 1). Participants who died without report of relapse were considered nonevents and censored at their last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc or PR disease assessment date + 1). Other participants who did not relapse during the study were considered nonevents and censored at the last relapse-free assessment date. Duration of CR was only applicable to participants with best overall response of CR.

CRc rate was defined as the number of participants who achieved the best response of CRc (CR,complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi) divided by the number of participants in the analysis population.

Transplantation rate is defined as the percentage of participants undergoing Hematopoietic stem cell transplant (HSCT) during the study period.

The Brief Fatigue Inventory (BFI) is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A global fatigue score can be obtained by averaging all the items on the BFI. The global BFI score will be calculated only if at least 5 of the 9 items are answered. A higher BFI fatigue score indicates worse outcome.

CRh rate was defined as the number of participants who achieved CRh at any of the postbaseline visits and did not have a best response of CR divided by the number of participants in the analysis population.

Transfusion conversion \& maintenance rate was defined for gilteritinib arm. Participants were classified as transfusion independent if there were no RBC or platelet transfusions within 28 days prior to the first dose to 28 days after the first dose; otherwise they were classified as transfusion dependent at baseline. Participants were considered independent postbaseline if they had 1 consecutive 8 week period without any RBC or platelet transfusion from 29 days after the first dose until the last dose date. For participants who were on treatment ≤ 4 weeks or \> 4 weeks but \< 12 weeks and there was no RBC or platelet transfusion within postbaseline period, they were considered not evaluable; otherwise, they were considered postbaseline transfusion dependent. Transfusion conversion rate was defined for participants who had evaluable postbaseline transfusion status. Transfusion status (independent vs. dependent) at baseline and postbaseline was reported in a 2 by 2 contingency table.

A treatment-emergent adverse event (TEAE) was defined as an AE observed after starting administration of the study drug (gilteritinib or salvage chemotherapy). If the AE occurred on day 1 and the onset check box was marked "Onset after first dose of study drug" or the onset check box was left blank, then the AE was considered treatment emergent. If the AE occurred on day 1 and the onset check box was marked "Onset before first dose of study drug", then the AE was not considered treatment emergent. Majority of salvage chemotherapy participants finished the study by cycle 2 of treatment, the duration of exposure was longer in the gilteritinib arm compared with the salvage chemotherapy arm (126.00 \[4.0, 885.0\] days versus 28.0 \[5.0, 217.0\] days). The NCI-CTCAE is defined as National Cancer Institute-Common Terminology Criteria for Adverse Events.

Astellas Pharma Global Development, Inc.

Salvage Chemotherapy

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Ethnicity

The category of "Other" includes those with cytogenetic risk status that cannot be categorized as favorable, intermediate or unfavorable.

Cytogenic Risk Status

ECOG performance status is a scale used to assess impact on daily activities. It is based on the investigator assessment. Scores range from 0 to 5, with 0-signifying fully active participant; 1-restricted in physically strenuous activity; 2-ambulatory and capable of all self-care, unable to work; 3-capable of only limited self-care, confined to bed more than 50% of waking hours; 4-completely disabled and 5-dead. Negative numerical score indicates an improvement and positive numerical score indicates a decline in participant's daily activities, indicating disease progression.

Baseline Eastern Cooperative Oncology Group (ECOG)

FLT3 Mutation Status by Central Testing by FLT3 CDx

Prior use of FLT3 inhibitor is defined as 'Yes' if participants received prior AML therapy of midostaurin, sorafenib or quizartinib; otherwise, prior use of FLT3 inhibitor is assigned as No.

Prior Use of FLT3 Inhibitor

Region

The analysis population was the ITT, with available data.

Baseline Body Surface Area (BSA)

Baseline Height

Baseline Weight

Primary refractory without HSCT

Relapse within 6 months after CRc and no HSCT

Relapse after 6 months after CRc and no HSCT

Relapse within 6 months after allogeneic HSCT

Relapse after 6 months after allogeneic HSCT

Response to First Line Therapy

High intensity chemotherapy

Low intensity chemotherapy

Preselected Salvage Chemotherapy

Primary refractory w/o HSCT, high intensity (IT)

Primary refractory w/o HSCT, low IT

Relapse w/I 6 mths after CRc and no HSCT, high IT

Relapse w/I 6 mths after CRc and no HSCT low IT

Relapse after 6 mths after CRc and no HSCT high IT

Relapse w/I 6 mths after allogeneic HSCT low IT

Relapse w/I 6 mths after allogeneic HSCT high IT

Relapse after 6 mths after allogeneic HSCT high IT

Relapse after 6 mths after CRc and no HSCT low IT

Relapse after 6 mths after allogeneic HSCT low IT

Baseline stratification factors. HSCT is hematopoietic stem cell transplant. CRc is composite complete remission.

Response to First Line Therapy-Preselected Salvage Chemotherapy

The analysis population was the Intention to Treatment (ITT), which consisted of all randomized participants.

Clinical Trial Disclosure

Stratified analysis where tratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT.

The analysis population was the Intention to Treatment (ITT) which consisted of all randomized participants.

Duration of Overall Survival (OS)

CR/CRh rate

CR rate

CRh rate

The analysis population was the response analysis set (RAS) which consisted of participants who were who were at least 112 days past the first dose of gilteritinib or randomization (for participants who did not receive gilteritinib). The participants were analyzed based on the randomized treatments.

Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm

Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT

Duration of Event-Free Survival (EFS)

Based on stratified Cochran-Mantel-Haenszel test. Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT. Treatment difference = gilteritinib -chemotherapy.

Percentage of Participants With Complete Remission (CR) Rate

The LFS was analyzed for participants who achieved remission using the stratified log-rank test with strata to control for response to first-line AML therapy and preselected salvage chemotherapy. Duration of LFS was based on Kaplan-Meier estimates.

The analysis population was the ITT, with participants with best response of CRc.

Duration of Leukemia-Free Survival (LFS)

The analysis population was the ITT, Duration of CR was only applicable to participants with best overall response of CR.

Duration of Remission

Treatment difference = gilteritinib - chemotherapy. The 95% CIs were asymptotic confidence limits using the normal approximation to the binomial distribution.

Percentage of Participants With Composite Complete Remission (CRc Rate)

Percentage of Participants Who Underwent Hematopoietic Stem Cell Transplant

C1D8: Using analysis of covariance (ANCOVA) including treatment as a fixed factor, baseline score, response to first-line AML therapy and preselected salvage chemotherapy per IRT as covariates. Least Square (LS) Mean difference was estimated using chemotherapy as control.

C2D1: Using analysis of covariance (ANCOVA) including treatment as a fixed factor, baseline score, response to first-line AML therapy and preselected salvage chemotherapy per IRT as covariates. Least Square (LS) Mean difference was estimated using chemotherapy as control.

Cycle 1 day 8 (C1D8)

Cycle 2 day 1 (C2D1)

The analysis population was the ITT, with participants with data at baseline.

Change From Baseline in Brief Fatigue Inventory (BFI)

Based on a stratified Cochran-Mantel-Haenszel test. Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per IRT. Pooled strata were used as shown in Table 12.3.3.2.

Treatment differences were adjusted based on pooled strata. Treatment difference = gilteritinib 120 mg - chemotherapy.

Percentage of Participants With Complete Remission (CR) With Partial Hematological Recovery (CRh)

Baseline Independent/ Post baseline Independent

Baseline Independent/Post baseline Dependent

Baseline Independent/Post baseline Not Evaluable

Baseline Dependent/Post baseline Independent

Baseline Dependent/Post baseline Dependent

Baseline Dependent/Post baseline Not Evaluable

The analysis population was the ITT, with participants who had evaluable postbaseline transfusion status.

Percentage of Participants Who Achieved Transfusion Conversion and Maintenance

Drug-related TEAE

Serious TEAE

Drug-related serious TEAE

TEAE leading to death

Drug-related TEAE leading to death

TEAE leading to withdrawal of treatment

Drug-related TEAE lead withdrawal of treatment

NCI-CTCAE Grade 3 or higher TEAE

Drug-related Grade 3 or higher TEAE

Death

The analysis population was the safety analysis set (SAF), which consisted of participants who received who received at least 1 dose of study drug (gilteritinib or salvage chemotherapy).

Number of Participants With Adverse Events

Overall Study

Daunorubicin

Midostaurin

Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given.

Consolidation: High-dose cytarabine and gilteritinib.

Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given.

Consolidation: High-dose cytarabine and midostaurin.

Induction: 120 mg orally daily x 14 days starting on day 8

Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles)

Induction: 50 mg orally twice daily x 14 days beginning on day 8

Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles)

First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3

Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3

Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1

Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1

Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles

Selena Luger, MD

Eligible untreated patients with FLT3 acute myeloid leukemia (AML) between the ages of 18 and 70 will be randomized to receive gilteritinib or midostaurin during induction and consolidation. Patients will also receive standard chemotherapy of daunorubicin and cytarabine during induction and high-dose cytarabine during consolidation.

Gilteritinib, is an oral drug that works by stopping the leukemia cells from making the FLT3 protein. This may help stop the leukemia cells from growing faster and thus may help make chemotherapy more effective. Gilteritinib has been approved by the Food and Drug Administration (FDA) for patients who have relapsed or refractory AML with a FLT3 mutation but is not approved by the FDA for newly diagnosed FLT3 AML, and its use in this setting is considered investigational.

Midostaurin is an oral drug that works by blocking several proteins on cancer cells, including FLT3 that can help leukemia cells grow. Blocking this pathway can cause death to the leukemic cells. Midostaurin is approved by the FDA for the treatment of FLT3 AML.

The purpose of this study is to compare the effectiveness of gilteritinib to midostaurin in patients receiving combination chemotherapy for FLT3 AML.

Approximately one third of patients with AML have a particular change in their leukemia cells (called a mutation) in a gene called FLT3. The presence of a FLT3 mutation can be used to direct treatment options.

This is an open-label phase II study. Patients will receive standard chemotherapy of daunorubicin and cytarabine during Induction and high-dose cytarabine during Consolidation. Patients will be randomized to gilteritinib or midostaurin. After approximately 90 patient's complete treatment, a review of the effectiveness of gliteritinib compared to midostaurin will be done. If gilteritinib is not as effective as midostaurin, the study may be stopped.

Bone marrow aspirate and biopsy will be done on Day 21 after start of Induction and after Induction to assess response. Patients with a complete response may proceed to consolidation chemotherapy. Another bone marrow aspirate and biopsy will be done after the first cycle of consolidation is complete.

Mandatory prescreening bone marrow and/or blood samples are required for FLT3 testing. Any left-over samples will be requested for future research (optional).

Mandatory bone marrow samples for research are required after Induction and if patient receives Consolidation, after the first cycle of Consolidation.

Open-Label, Randomized trial of Daunorubicin/Cytarabine and High Dose Cytarabine + Gilteritinib vs Midostaurin for Induction and Consolidation. FLT3 mutated patients will be stratified based on TKD vs ITD. Patients who are FLT3 ITD will be further stratified by Signal Ratio (high vs. low of FLT3 Wild Type) and Nucleophosmin 1-Mutated (NPM1) \[positive vs negative\].

Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia

Randomized Trial of Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (AML)

CRc evaluated by polymerase chain reaction (PCR) at the end of Induction

CR evaluated by FLT3 testing after Induction

MRD- CRc evaluated by flow cytometry after Induction

CRc assessed in accordance with 2017 European LeukemiaNet (ELN)

Number of participants with abnormal laboratory values and/or adverse events

Astellas Pharma Inc

PrECOG, LLC.

Hematinics

Iron-Dextran Complex

Gemtuzumab

Staurosporine

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Phase I (Trial part MODULE): The treatment plan combines increasing doses levels of midostaurin (25/50 mg BID) and gemtuzumab ozogamicin (3 mg/m\^2 i.v. max 4.5 mg on day(s) 1, (4, 7)) with 7+3 standard chemotherapy scheme using cytarabine (200 mg/m\^2 cont. inf. i.v. on days 1 to 7) and daunorubicin (60 mg/m\^2 i.v. on days 1 to 3).

Phase II (Trial part MAGNOLIA): midostaurin (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus GO (recommended phase II dose, RP2D) in CBF AML

Phase II (Trial part MAGNOLIA): treatment standard of CBF AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v. plus GO (3 mg/m\^2 i.v. max 4.5 mg) on days 1, 4, 7). No additional Midostaurin is given.

Phase II (Trial part MAGMA): GO (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus Midostaurin (recommended phase II dose, RP2D) in FLT3 mutated AML

Phase II Trial (MAGMA): treatment standard of FLT3 mutated AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v plus midostaurin). No additional GO is given.

Midostaurin (IMP) induction: 25 mg or 50 mg peroral BID, days 8 to 21 depending on assigned dose level

GO (IMP) induction: 3 mg/m\^2 i.v. max 4.5 mg, on day1, or on days 1, 4, or days 1, 4, 7 depending on assigned dose level

Daunorubicin (DNR, non-IMP) induction: 60 mg/m\^2/day i.v., days 1 to 3

Cytarabine (AraC, non-IMP) induction: 200 mg/m\^2/day cont. infusion, days 1 to 7

MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GO

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles;

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2 i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GO

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg on days 1, 4, 7; 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21, induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles;

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycles 1-2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGMA-trial:GO associated with conventional chemotherapy (AraC+DNR)+Midostaurin

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation	NCT02421939	Leukemia, Acute...	gilteritinib LoDAC (Low Dose... Azacitidine MEC (Mitoxantro... FLAG-IDA (Granu...	18 Years -	Astellas Pharma Inc
Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia	NCT03836209	Acute Myeloid L...	Gilteritinib Midostaurin Daunorubicin Cytarabine	18 Years - 70 Years	PrECOG, LLC.
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)	NCT04385290	Acute Myeloid L...	MODULE: convent... MAGNOLIA-trial:... MAGNOLIA-trial:... MAGMA-trial:GO ... MAGMA-trial: co...	18 Years - 75 Years	Technische Universität Dresden
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation	NCT02421939	Leukemia, Acute...	gilteritinib LoDAC (Low Dose... Azacitidine MEC (Mitoxantro... FLAG-IDA (Granu...	18 Years -	Astellas Pharma Inc
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation	NCT02421939	Leukemia, Acute...	gilteritinib LoDAC (Low Dose... Azacitidine MEC (Mitoxantro... FLAG-IDA (Granu...	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for flt3 mutation