Clinical Trials List
Protocol NumberCPKC412A2220
NCT Number(ClinicalTrials.gov Identfier)NCT03280030
Completed
2017-12-01 - 2023-12-31
Phase II
Terminated4
ICD-10C92.90
Myeloid leukemia, unspecified, not having achieved remission
A Phase II, Randomized, Double-blind, Multi-center, Placebo-controlled Study to Evaluate the Efficacy and Safety of Twice Daily Oral Midostaurin in Combination With Daunorubicin/Cytarabine Induction, High-dose Cytarabine Consolidation, and Midostaurin Single Agent Continuation Therapy in Newly Diagnosed Patients With FLT3-mutated Acute Myeloid Leukemia (AML).
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2026/04/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Co-Principal Investigator
- Po-Nan Wang Division of Hematology & Oncology
- Hung Chang 未分科
- 高小雯 Division of Hematology & Oncology
- 張 鴻 Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Huai-Hsuan Huang Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- 李啟誠 Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- Jih-Luh Tang 未分科
- Tsung -Chih Chen Division of Hematology & Oncology
- Chien-Chin Lin Division of Others -
- 劉家豪 Division of Hematology & Oncology
- 徐思淳 未分科
- - - Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
Primary Objective:
● Safety evaluation part (Part 1): To evaluate the safety and tolerability of
midostaurin in combination with daunorubicin/cytarabine induction and high-dose
cytarabine consolidation in Japanese patients with newly diagnosed AML.
● Randomized part (Part 2): To evaluate the efficacy based on event-free survival
of midostaurin versus placebo in combination with daunorubicin/cytarabine
induction, with high-dose cytarabine consolidation, and with midostaurin single
agent continuation therapy in newly diagnosed patients with FLT3-mutated AML.
Test Drug
Rydapt
Active Ingredient
Midostaurin (PKC412)
Dosage Form
Capsule
Dosage
25
Endpoints
Efficacy assessments
Bone marrow aspirate and peripheral blood specimens will be evaluated for
remission versus persistent or relapsed disease (Progressive Disease) according to
Cheson criteria.
The following responses will be collected:
Safety assessments
● Physical examination
● ECOG PS
● Weight and vital signs
● 12-lead ECG
● MUGA, ECHO
● Laboratory assessments including hematology, chemistry, coagulation and
urinalysis
● Adverse events (AEs) with severity, relationship to study treatment and
seriousness
● Complete remission (CR)
● Morphologic complete remission with incomplete platelet count recovery (CRp)
● Partial Remission (PR)
● Treatment Failure
● Relapse after CR
Other assessments
● PK parameters
Plasma concentrations of midostaurin and its active metabolites CGP62221 and
CGP52421 will be measured using a validated liquid chromatography-tandem mass
spectrometry (LC-MS/MS) assay with a lower limit of quantification (LLOQ) of
approximately 10.0 ng/mL.
● Exploratory biomarker assessments
Exploratory biomarker analyses will be conducted to investigate potential
biomarkers associated with response or resistance to treatment. This will include
exploration of potential predictive/ pharmacodynamics markers and measurement of
MRD levels.
● Patient reported outcomes assessment by the European Organization for
Research and Treatment of Cancer quality of life (EORTC QLQ-C30)
● Healthcare resource utilization
Resource utilization data will be collected for all patients when they come in for site
visits. This data will be used to support health economic evaluations. Data includes
the number and duration of hospitalization for patients, reason for hospitalization,
and type of hospital facility (e.g., emergency department, intensive care unit, general
ward unit, etc.).
Bone marrow aspirate and peripheral blood specimens will be evaluated for
remission versus persistent or relapsed disease (Progressive Disease) according to
Cheson criteria.
The following responses will be collected:
Safety assessments
● Physical examination
● ECOG PS
● Weight and vital signs
● 12-lead ECG
● MUGA, ECHO
● Laboratory assessments including hematology, chemistry, coagulation and
urinalysis
● Adverse events (AEs) with severity, relationship to study treatment and
seriousness
● Complete remission (CR)
● Morphologic complete remission with incomplete platelet count recovery (CRp)
● Partial Remission (PR)
● Treatment Failure
● Relapse after CR
Other assessments
● PK parameters
Plasma concentrations of midostaurin and its active metabolites CGP62221 and
CGP52421 will be measured using a validated liquid chromatography-tandem mass
spectrometry (LC-MS/MS) assay with a lower limit of quantification (LLOQ) of
approximately 10.0 ng/mL.
● Exploratory biomarker assessments
Exploratory biomarker analyses will be conducted to investigate potential
biomarkers associated with response or resistance to treatment. This will include
exploration of potential predictive/ pharmacodynamics markers and measurement of
MRD levels.
● Patient reported outcomes assessment by the European Organization for
Research and Treatment of Cancer quality of life (EORTC QLQ-C30)
● Healthcare resource utilization
Resource utilization data will be collected for all patients when they come in for site
visits. This data will be used to support health economic evaluations. Data includes
the number and duration of hospitalization for patients, reason for hospitalization,
and type of hospital facility (e.g., emergency department, intensive care unit, general
ward unit, etc.).
Inclution Criteria
Patients eligible for inclusion in this study must meet all of the following eligibility
criteria:
1. Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016
classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA
are not eligible
2. Documented presence of an ITD and/or TKD activating mutation in the FLT3
gene, as determined by analysis in a Novartis designated laboratory
An exception will be patients who are enrolled into the part 1 in Japan, who may be
treated with midostaurin irrespective of AML FLT3 genotype
3. Age ≥ 20 years, < 65 years of age
4. AML patients with a history of antecedent myelodysplasia (MDS) remain eligible
for treatment on this trial but must not have received prior cytotoxic therapy (e.g.,
azacytidine or decitabine)
5. Patients must meet the following laboratory value criteria that indicate adequate
organ function at the screening visit:
● Serum creatinine < 1.5 mg/dL
● Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert
syndrome
● Aspartate transaminase (AST) ≤ 3.0 x ULN
● Alanine transaminase (ALT) ≤ 3.0 x ULN
6. Written informed consent must be obtained prior to any screening procedures.
For patients in Japan less than 20 years of age, written consent is required from the
patient as well as from their legal representative.
criteria:
1. Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016
classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA
are not eligible
2. Documented presence of an ITD and/or TKD activating mutation in the FLT3
gene, as determined by analysis in a Novartis designated laboratory
An exception will be patients who are enrolled into the part 1 in Japan, who may be
treated with midostaurin irrespective of AML FLT3 genotype
3. Age ≥ 20 years, < 65 years of age
4. AML patients with a history of antecedent myelodysplasia (MDS) remain eligible
for treatment on this trial but must not have received prior cytotoxic therapy (e.g.,
azacytidine or decitabine)
5. Patients must meet the following laboratory value criteria that indicate adequate
organ function at the screening visit:
● Serum creatinine < 1.5 mg/dL
● Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert
syndrome
● Aspartate transaminase (AST) ≤ 3.0 x ULN
● Alanine transaminase (ALT) ≤ 3.0 x ULN
6. Written informed consent must be obtained prior to any screening procedures.
For patients in Japan less than 20 years of age, written consent is required from the
patient as well as from their legal representative.
Exclusion Criteria
Patients eligible for this study must not meet any of the following criteria:
1. Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has
been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts
are not eligible
2. Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy
for another cancer or disorder
3. isolated extramedullary leukemia (please refer to protocol Section 7.2.2.1)
4. Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of
the excipients of midostaurin/placebo, cytarabine or daunorubicin
5. Any investigational agent within 30 days or 5 half-lives, whichever is greater,
prior to Day 1. An investigational agent is defined as an agent with no approved
medical use in adults or in pediatric patients
6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)
7. Strong CYP3A4/5 enzyme inducing drugs (e.g., phenytoin, clarithromycin,
telithromycin, carbamazepine, rifampin, rifabutin, phenobarbitol, St. John’s Wort)
8. Prior chemotherapy for leukemia or myelodysplasia. However, the following prior
therapies are allowed:
a. Emergency leukapheresis
b. Emergency treatment for hyperleukocytosis with hydroxyurea for 7 days
c. Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis
(one dose only)
d. Hematopoietic growth factor/cytokine support
9. Any surgical procedure, excluding central venous catheter placement or other
minor procedures (e.g., skin or bone marrow biopsy) within 14 days prior to Day 1
10. Any other known disease or concurrent severe and/or uncontrolled medical
condition (e.g., cardiovascular disease including congestive heart failure or active
uncontrolled infection) that could compromise participation in the study
11. Abnormal chest X-ray unless the abnormality represents a non-active, or nonclinically significant finding, such as scarring
12. Known impairment of gastrointestinal (GI) function or GI disease that might alter
significantly the absorption of midostaurin
13. Known confirmed diagnosis of human immunodeficiency virus (HIV)
14. Evidence of active HBV or HCV viral infection (confirmed by peripheral blood
viral load). Patients with positive serology results indicative of high risk for viral
reactivation must have negative viral load results within 28 days prior to Day 1
15. Cardiac or cardiac repolarization abnormality, including any of the following:
● History of myocardial infarction (MI), angina pectoris, coronary artery
bypass graft (CABG) within 6 months prior to Day 1
● Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),
complete left bundle branch block, high-grade AV block (e.g., bifascicular block,
Mobitz type II and third degree AV block)
● Uncontrolled congestive heart failure
● Left ventricular ejection fraction of <50%
● Poorly controlled hypertension
● QTcF at screening > 470 ms
● Long QT syndrome, family history of idiopathic sudden death or congenital
long QT syndrome, or any of the following:
● Risk factors for torsades de pointe (TdP) including uncorrected
hypokalemia or hypomagnesemia, history of cardiac failure, or history of
clinically significant/symptomatic bradycardia
● Concomitant medication(s) with a known risk of torsades de
pointes that cannot be discontinued or replaced safely with an alternative
medication
● Inability to determine the QTcF interval
16. Pregnant or nursing (lactating) women
17. Women of child-bearing potential, unless they are using highly effective methods
of contraception during dosing and for 4 months after stopping medication
18. Sexually active males unless they use a condom during intercourse while taking
the drug during treatment and for 4 months after stopping treatment and should not
father a child in this period
1. Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has
been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts
are not eligible
2. Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy
for another cancer or disorder
3. isolated extramedullary leukemia (please refer to protocol Section 7.2.2.1)
4. Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of
the excipients of midostaurin/placebo, cytarabine or daunorubicin
5. Any investigational agent within 30 days or 5 half-lives, whichever is greater,
prior to Day 1. An investigational agent is defined as an agent with no approved
medical use in adults or in pediatric patients
6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)
7. Strong CYP3A4/5 enzyme inducing drugs (e.g., phenytoin, clarithromycin,
telithromycin, carbamazepine, rifampin, rifabutin, phenobarbitol, St. John’s Wort)
8. Prior chemotherapy for leukemia or myelodysplasia. However, the following prior
therapies are allowed:
a. Emergency leukapheresis
b. Emergency treatment for hyperleukocytosis with hydroxyurea for 7 days
c. Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis
(one dose only)
d. Hematopoietic growth factor/cytokine support
9. Any surgical procedure, excluding central venous catheter placement or other
minor procedures (e.g., skin or bone marrow biopsy) within 14 days prior to Day 1
10. Any other known disease or concurrent severe and/or uncontrolled medical
condition (e.g., cardiovascular disease including congestive heart failure or active
uncontrolled infection) that could compromise participation in the study
11. Abnormal chest X-ray unless the abnormality represents a non-active, or nonclinically significant finding, such as scarring
12. Known impairment of gastrointestinal (GI) function or GI disease that might alter
significantly the absorption of midostaurin
13. Known confirmed diagnosis of human immunodeficiency virus (HIV)
14. Evidence of active HBV or HCV viral infection (confirmed by peripheral blood
viral load). Patients with positive serology results indicative of high risk for viral
reactivation must have negative viral load results within 28 days prior to Day 1
15. Cardiac or cardiac repolarization abnormality, including any of the following:
● History of myocardial infarction (MI), angina pectoris, coronary artery
bypass graft (CABG) within 6 months prior to Day 1
● Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),
complete left bundle branch block, high-grade AV block (e.g., bifascicular block,
Mobitz type II and third degree AV block)
● Uncontrolled congestive heart failure
● Left ventricular ejection fraction of <50%
● Poorly controlled hypertension
● QTcF at screening > 470 ms
● Long QT syndrome, family history of idiopathic sudden death or congenital
long QT syndrome, or any of the following:
● Risk factors for torsades de pointe (TdP) including uncorrected
hypokalemia or hypomagnesemia, history of cardiac failure, or history of
clinically significant/symptomatic bradycardia
● Concomitant medication(s) with a known risk of torsades de
pointes that cannot be discontinued or replaced safely with an alternative
medication
● Inability to determine the QTcF interval
16. Pregnant or nursing (lactating) women
17. Women of child-bearing potential, unless they are using highly effective methods
of contraception during dosing and for 4 months after stopping medication
18. Sexually active males unless they use a condom during intercourse while taking
the drug during treatment and for 4 months after stopping treatment and should not
father a child in this period
The Estimated Number of Participants
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Taiwan
20 participants
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Global
63 participants
