A Phase 3 interventional study of Midostaurin and Cytarabine in Acute Myeloid Leukemia, sponsored by Novartis Pharmaceuticals. Completed at 86 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-29.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
The purpose of this study was to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who were eligible for standard induction and consolidation
This Phase IIIb study was designed as a single arm study and allowed the assessment of variation of the "7+3" regimen in an extended patient population compared to RATIFY (higher dose of daunorubicin (60-90 mg/m2/day), the substitution of daunorubicin by idarubicin (12mg/m2/day), and lower dose of cytarabine (100-200 mg/m2/day) and the "5+2" reduced dose regimen). Safety was the primary endpoint. Complete Response (CR)/Complete remission with incomplete hematological recovery (CRi) in induction, consolidation and maintenance therapy was collected as secondary endpoint.
Patients who were newly diagnosed with AML, had a known FLT3 ITD (Internal tandem duplication) or TKD (Tyrosine kinase domain)(, mutation and had recently started on "7+3" or "5+2" in induction and high dose of cytarabine in consolidation were consented and screened for the clinical study.
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The protocol treatment allowed the following treatment phases:
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's enrollment of 301 is above the median of 40 across 3,005 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients eligible for inclusion in this study have to meet all of the following criteria:
Exclusion criteria:
Patients eligible for this study must not meet any of the following criteria:
Prior therapy for AML with the following exceptions:
Pregnancy statements and requirements:
Women of , defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 4 months after stopping medication. Highly effective contraception methods include:
In case of use of oral contraception women should also add a barrier method of contraception, particularly as it is currently unknown whether midostaurin may reduce the effectiveness of hormonal contraceptives.
Sexually-active males unless they use a condom during intercourse with females of or pregnant women and for at least 4 months after stopping treatment to avoid conception or embryo-fetal harm.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients went through 3 phases: Induction phase - Day (D)8 to D28 in combination with standard of care (7+3 or 5+2 chemotherapy) up to 2 cycles; Consolidation phase - D8 to D28 in combination with cytarabine up to 4 cycles; Maintenance phase - D1 to D28 up to 12 cycles
Drug: Midostaurin · Drug: Cytarabine · Drug: anthracycline ((daunorubicin or idarubicin): Induction Phase only
Induction Phase: 50 mg (two 25 mg capsules) twice a day by mouth on days 8-28, for 1 - 2 cycles; a cycle = 28 days; Consolidation Phase: 50 mg (two 25 mg capsules) twice a day by mouth on days 8-28, for up to 4 cycles; Maintenance Phase: Continuous dosing (days 1 - 28) for up yo 12 cycles or until relapse, unacceptable toxicity, death, physician's decision, subject/guardian decision, protocol deviation, study termination by Sponsor, lost to follow-up, technical problems, pregnancy, subject withdrew consent, or until the end of study, whichever event occurred first.
Also known as: PKC412
Induction Phase (standard dose) (7 + 3 arm): 100-200 mg/m2/day by Continuous intravenous infusion (CIVI) days 1-7 (168 hours infusion); Induction Phase (5 + 2 arm): 100 mg/m2/day by CIVI days 1-5; Consolidation Phase: 1-3 g/m2 infusion over 3 hours every 12 h on days 1, 3 and 5, up to 4 cycles based on age and per investigator discretion
daunorubicin (7 + 3 arm): 60-90 mg/m2/day by IV push on days 1-3 (with standard-dose cytarabine); daunorubicin (5 + 2 arm): 60 mg/m2/day by IV push on days 1-2; idarubicin (7 + 3 arm): 12 mg/m2/day by IV push on days 1-3 (with standard-dose cytarabine); idarubicin (5 + 2 arm): 12 mg/m2/day by IV push on days 1-2
Percentage of Patients With Adverse Events (AEs), Grade 3 & 4 AEs, Serious Adverse Events (SAEs), AEs Leading to Discontinuation, and Deaths up to 24 Months (M24).
Safety of Midostaurin was represented by various types of AEs, SAEs \& death up to M24. AE: the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. AE grades to characterize the severity of AEs were based on the Common Terminology Criteria for AEs ver. 4.03 with Grade (Gr) 1: mild; Gr 2: moderate; Gr 3: severe; Gr 4: life-threatening; Gr 5: death related to AE. AEs not related to hematological toxicities were generally of grade 1 or 2 severity. SAE: 1 of the following: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, i.e. an event that jeopardizes the patient or may require medical or surgical intervention to prevent 1 of the outcomes listed above, requires inpatient hospitalization or prolongation of existing hospitalization with a few exceptions.
Time frame: Baseline up to approximatly 24 months
Percentage of Patients With Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (CRi) as Per Local Assessment
CR/CRi rate is defined as the percentage of patients with complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) as per local assessment in Induction, Consolidation and Maintenance phases. CR/CRi rate was calculated based on the full analysis set (FAS). Complete remission (CR): Bone marrow blasts \<5% with spicules; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0 x109/L; platelet count \>100 x 109/L; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 x109/L) or thrombocytopenia (\<100 x 109/L)
Time frame: Baseline up to approximately 24 months
Participants took part in 88 investigative sites in 15 countries.
| Milestone | Midostaurin |
|---|---|
| Started | 301 |
| Entered induction phase | 301 |
| Entered consolidation phase | 210 |
| Entered maintenance phase | 93 |
| Completed | 52 |
| Not completed | 249 |
| Withdrew: Lack of efficacy | 73 |
| Withdrew: Adverse event | 32 |
| Withdrew: Death | 18 |
| Withdrew: Patient/guardian decision | 17 |
| Withdrew: Physician decision | 104 |
| Withdrew: Protocol violation | 4 |
| Withdrew: Lost to follow-up | 1 |
Safety of Midostaurin was represented by various types of AEs, SAEs \& death up to M24. AE: the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. AE grades to characterize the severity of AEs were based on the Common Terminology Criteria for AEs ver. 4.03 with Grade (Gr) 1: mild; Gr 2: moderate; Gr 3: severe; Gr 4: life-threatening; Gr 5: death related to AE. AEs not related to hematological toxicities were generally of grade 1 or 2 severity. SAE: 1 of the following: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, i.e. an event that jeopardizes the patient or may require medical or surgical intervention to prevent 1 of the outcomes listed above, requires inpatient hospitalization or prolongation of existing hospitalization with a few exceptions.
| Participants | Midostaurin |
|---|---|
| Adverse events (AEs) - all grades | 295 |
| Grade >=3 AEs | 254 |
| Serious adverse events (SAEs) - all grades | 137 |
| AEs leading to discontinuation - all grades | 40 |
| Deaths | 19 |
CR/CRi rate is defined as the percentage of patients with complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) as per local assessment in Induction, Consolidation and Maintenance phases. CR/CRi rate was calculated based on the full analysis set (FAS). Complete remission (CR): Bone marrow blasts \<5% with spicules; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0 x109/L; platelet count \>100 x 109/L; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 x109/L) or thrombocytopenia (\<100 x 109/L)
| Participants | Midostaurin |
|---|---|
| Complete remission (CR) | 196 |
| Complete remission with incomplete recovery (CRi) | 46 |
Collected over Adverse Events were reported from first dose of study treatment until end of treatment plus 30 days, up to a maximum duration of 25 months (24 months plus 1 month (30 days) post treatment).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Induction Phase | 16/301 (5.3%) | 76/301 (25.2%) | 253/301 (84.1%) |
| Consolidation Phase | 3/210 (1.4%) | 67/210 (31.9%) | 179/210 (85.2%) |
| Maintenance Phaase | 0/93 (0%) | 7/93 (7.5%) | 48/93 (51.6%) |
| Overall | 19/301 (6.3%) | 137/301 (45.5%) | 277/301 (92%) |
| Event | Induction Phase | Consolidation Phase | Maintenance Phaase | Overall |
|---|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 6/301 | 26/210 | 0/93 | 32/301 |
| SepsisInfections and infestations | 4/301 | 11/210 | 0/93 | 14/301 |
| PneumoniaInfections and infestations | 9/301 | 3/210 | 1/93 | 13/301 |
| Septic shockInfections and infestations | 5/301 | 6/210 | 0/93 | 11/301 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 5/301 | 2/210 | 0/93 | 7/301 |
| CytopeniaBlood and lymphatic system disorders | 0/301 | 4/210 | 0/93 | 4/301 |
| ColitisGastrointestinal disorders | 5/301 | 0/210 | 0/93 | 5/301 |
| PyrexiaGeneral disorders | 0/301 | 3/210 | 0/93 | 3/301 |
| Atrial fibrillationCardiac disorders | 4/301 | 0/210 | 0/93 | 4/301 |
| LeukocytosisBlood and lymphatic system disorders | 0/301 | 0/210 | 1/93 | 1/301 |
| Event | Induction Phase | Consolidation Phase | Maintenance Phaase | Overall |
|---|---|---|---|---|
| PyrexiaGeneral disorders | 93/301 | 72/210 | 3/93 | 139/301 |
| DiarrhoeaGastrointestinal disorders | 97/301 | 40/210 | 8/93 | 121/301 |
| NauseaGastrointestinal disorders | 76/301 | 67/210 | 18/93 | 121/301 |
| Febrile neutropeniaBlood and lymphatic system disorders | 67/301 | 44/210 | 0/93 | 88/301 |
| StomatitisGastrointestinal disorders | 54/301 | 25/210 | 0/93 | 72/301 |
| NeutropeniaBlood and lymphatic system disorders | 33/301 | 50/210 | 12/93 | 70/301 |
| VomitingGastrointestinal disorders | 57/301 | 33/210 | 3/93 | 69/301 |
| HeadacheNervous system disorders | 24/301 | 47/210 | 3/93 | 59/301 |
| ConstipationGastrointestinal disorders | 32/301 | 41/210 | 2/93 | 65/301 |
| RashSkin and subcutaneous tissue disorders | 38/301 | 29/210 | 3/93 | 64/301 |
All enrolled subjects set comprises all screened subjects who are not screening failures.
| Age, Continuous(years) | Midostaurin |
|---|---|
| Mean | 55.8 ± 13.82 |
| Sex: Female, Male(Participants) | Midostaurin |
|---|---|
| Female | 160 |
| Male | 141 |
| Race/Ethnicity, Customized(Participants) | Midostaurin |
|---|---|
| White | 225 |
| Other | 18 |
| Unknown | 56 |
| Missing | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Data sharing details ↗ · www.clinicalstudydatarequest.com
Ran from Feb 2018 to primary completion in Jul 2021, 40 months.
Results were first posted in Feb 2024, 2 years 6 months after primary completion.
Of 42 industry-sponsored phase 3 interventional studies under Leukemia, Myeloid, Acute, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 62. This study's 40 months is close to that.
Counting every sponsor, half of 120 studies reached it within 74 months; a quarter within 39 and three quarters within 99.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Midostaurin