Clinical Trials List
Protocol Number2215-CL-0301
NCT Number(ClinicalTrials.gov Identfier)NCT02421939
2015-08-01 - 2020-03-31
Phase III
Terminated8
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
ICD-10C92
Myeloid leukemia
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
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Astellas Pharma Global Development, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yu-Min Yeh Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 楊陽生 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 高小雯 Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
- Po-Nan Wang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- MING YAO Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 徐思淳 Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- - - 未分科
- Chien-Yuan Chen Division of Hematology & Oncology
- 陳尹愷 Division of Hematology & Oncology
- 劉家豪 Division of Hematology & Oncology
- SHAN-CHI YU 未分科
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
The primary objective is to:
Determine the clinical benefit of ASP2215 therapy in subjects with FMS-like tyrosine kinase
(FLT3) mutated AML who are refractory to or have relapsed after first-line AML therapy as
shown with overall survival (OS) compared to salvage chemotherapy.
The key secondary objectives are to:
Determine the overall efficacy in event-free survival (EFS) of ASP2215 compared to salvage
chemotherapy.
Determine the overall efficacy in complete remission (CR) rate of ASP2215 compared to salvage
chemotherapy.
Test Drug
ASP2215 Down-sized Tablets 40 mg
Active Ingredient
ASP2215
Dosage Form
tablet
Dosage
40mg
Endpoints
Primary Efficacy Endpoint:
OS
Key Secondary Efficacy Endpoints:
EFS
CR
Secondary Efficacy Endpoints:
LFS
Duration of remission
CRc (CR + CRi + CRp)
Transplantation
BFI
Exploratory Endpoints:
PGx
FLT3 gene mutation status
o mutation types and frequency
o relationship to efficacy and safety
o mechanisms of acquired resistance
Exploratory (predictive) biomarkers of ASP2215 activity
Resource utilization including hospitalization, blood transfusion, antibiotic iv infusions,
medication for AEs and opioid usage
FACIT-Dys-SF
FACT-Leu and dizziness and mouth sore items
EQ-5D-5L
Safety endpoints
AEs
Serum chemistry, hematology, coagulation and urinalysis
Vital signs
Ophthalmologic assessments
ECGs
ECOG performance scores
Pharmacokinetics
ASP2215 concentration in blood
OS
Key Secondary Efficacy Endpoints:
EFS
CR
Secondary Efficacy Endpoints:
LFS
Duration of remission
CRc (CR + CRi + CRp)
Transplantation
BFI
Exploratory Endpoints:
PGx
FLT3 gene mutation status
o mutation types and frequency
o relationship to efficacy and safety
o mechanisms of acquired resistance
Exploratory (predictive) biomarkers of ASP2215 activity
Resource utilization including hospitalization, blood transfusion, antibiotic iv infusions,
medication for AEs and opioid usage
FACIT-Dys-SF
FACT-Leu and dizziness and mouth sore items
EQ-5D-5L
Safety endpoints
AEs
Serum chemistry, hematology, coagulation and urinalysis
Vital signs
Ophthalmologic assessments
ECGs
ECOG performance scores
Pharmacokinetics
ASP2215 concentration in blood
Inclution Criteria
Inclusion Criteria
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved
written Informed Consent and privacy language as per national regulations (e.g., Health
Insurance Portability and Accountability Act [HIPAA] Authorization for United States
sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing
informed consent.
3. Subject has a diagnosis of primary AML or AML secondary to MDS according to World
Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by
pathology review at the treating institution.
4. Subject is refractory to or relapsed after first-line AML therapy (with or without HSCT).
● Refractory to first-line AML therapy is defined as:
a. Subject did not achieve CR/CRi/CRp under initial therapy. A subject eligible
for standard therapy must receive at least 1 cycle of an anthracycline containing
induction block in standard dose for the selected induction regimen. A subject
not eligible for standard therapy must have received at least 1 complete block
of induction therapy seen as the optimum choice of therapy to induce remission
for this subject as per investigator’s assessment.
● Untreated first hematologic relapse is defined as:
a. Subject must have achieved a CR/CRi/CRp (as defined by [Cheson et al,
2003], see Section 5.3) with first-line treatment and has hematologic relapse.
5. Subject is positive for FLT3 activating mutation in bone marrow or whole blood as
determined by central lab. In the investigator’s opinion, a subject with rapidly
proliferative disease and unable to wait for the central lab results can be enrolled based
on local tests.
6. Subject has an ECOG performance status ≤ 2.
7. Subject is eligible for preselected salvage chemotherapy according to investigator
assessment.
8. Subject must meet the following criteria as indicated on the clinical laboratory tests:
● Serum AST and ALT ≤ 2.5 x upper limit of normal (ULN)
● Serum total bilirubin (TBL) ≤ 1.5 x ULN
● Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of
> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9. Subject is suitable for oral administration of study drug.
10. Female subject must either:
● Be of nonchild bearing potential:
● postmenopausal (defined as at least 1 year without any menses) prior to
screening, or
● documented surgically sterile (at least 1 month prior to screening)
● Or, if of childbearing potential,
● Agree not to try to become pregnant during the study and for 45 days after the
final study drug administration
● And have a negative urine pregnancy test at screening
● And, if heterosexually active, agree to consistently use 2 forms of highly
effective birth control† (at least 1 of which must be a barrier method) starting at
screening and throughout the study period and for 45 days after the final study
drug administration.
11. Female subject must agree not to breastfeed at screening and throughout the study period
and for 45 days after the final study drug administration.
12. Female subject must not donate ova starting at screening and throughout the study period
and for 45 days after the final study drug administration.
13. Male subject and their female spouse/partners who are of childbearing potential must be
using highly effective contraception consisting of 2 forms of birth control† (at least 1 of
which must be a barrier method) starting at screening and continue throughout the study
period and for 105 days after the final study drug administration.
†Highly effective forms of birth control include:
● Consistent and correct usage of established oral contraception.
● Established intrauterine device or intrauterine system.
● Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (spermicidal
foam/gel/film/cream/suppository is not applicable to sites in Japan)
● Calendar-based contraceptive methods (Knaus-Ogino or rhythm method applicable to
sites in Japan only)
14. Male subject must not donate sperm starting at screening and throughout the study period
and 105 days after the final study drug administration
15. Subject agrees not to participate in another interventional study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved
written Informed Consent and privacy language as per national regulations (e.g., Health
Insurance Portability and Accountability Act [HIPAA] Authorization for United States
sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing
informed consent.
3. Subject has a diagnosis of primary AML or AML secondary to MDS according to World
Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by
pathology review at the treating institution.
4. Subject is refractory to or relapsed after first-line AML therapy (with or without HSCT).
● Refractory to first-line AML therapy is defined as:
a. Subject did not achieve CR/CRi/CRp under initial therapy. A subject eligible
for standard therapy must receive at least 1 cycle of an anthracycline containing
induction block in standard dose for the selected induction regimen. A subject
not eligible for standard therapy must have received at least 1 complete block
of induction therapy seen as the optimum choice of therapy to induce remission
for this subject as per investigator’s assessment.
● Untreated first hematologic relapse is defined as:
a. Subject must have achieved a CR/CRi/CRp (as defined by [Cheson et al,
2003], see Section 5.3) with first-line treatment and has hematologic relapse.
5. Subject is positive for FLT3 activating mutation in bone marrow or whole blood as
determined by central lab. In the investigator’s opinion, a subject with rapidly
proliferative disease and unable to wait for the central lab results can be enrolled based
on local tests.
6. Subject has an ECOG performance status ≤ 2.
7. Subject is eligible for preselected salvage chemotherapy according to investigator
assessment.
8. Subject must meet the following criteria as indicated on the clinical laboratory tests:
● Serum AST and ALT ≤ 2.5 x upper limit of normal (ULN)
● Serum total bilirubin (TBL) ≤ 1.5 x ULN
● Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of
> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9. Subject is suitable for oral administration of study drug.
10. Female subject must either:
● Be of nonchild bearing potential:
● postmenopausal (defined as at least 1 year without any menses) prior to
screening, or
● documented surgically sterile (at least 1 month prior to screening)
● Or, if of childbearing potential,
● Agree not to try to become pregnant during the study and for 45 days after the
final study drug administration
● And have a negative urine pregnancy test at screening
● And, if heterosexually active, agree to consistently use 2 forms of highly
effective birth control† (at least 1 of which must be a barrier method) starting at
screening and throughout the study period and for 45 days after the final study
drug administration.
11. Female subject must agree not to breastfeed at screening and throughout the study period
and for 45 days after the final study drug administration.
12. Female subject must not donate ova starting at screening and throughout the study period
and for 45 days after the final study drug administration.
13. Male subject and their female spouse/partners who are of childbearing potential must be
using highly effective contraception consisting of 2 forms of birth control† (at least 1 of
which must be a barrier method) starting at screening and continue throughout the study
period and for 105 days after the final study drug administration.
†Highly effective forms of birth control include:
● Consistent and correct usage of established oral contraception.
● Established intrauterine device or intrauterine system.
● Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (spermicidal
foam/gel/film/cream/suppository is not applicable to sites in Japan)
● Calendar-based contraceptive methods (Knaus-Ogino or rhythm method applicable to
sites in Japan only)
14. Male subject must not donate sperm starting at screening and throughout the study period
and 105 days after the final study drug administration
15. Subject agrees not to participate in another interventional study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
Exclusion Criteria
Exclusion Criteria
Subject will be excluded from participation if any of the following apply:
1. Subject was diagnosed as acute promyelocytic leukemia.
2. Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
3. Subject has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
4. Subject is in second or later hematologic relapse or has received salvage therapy for
refractory disease.
5. Subject has clinically active central nervous system leukemia.
6. Subject has been diagnosed with another malignancy, unless disease-free for at least
5 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study
if definitive treatment for the condition has been completed. Subjects with organ-confined
prostate cancer with no evidence of recurrent or progressive disease are eligible if
hormonal therapy has been initiated or the malignancy has been surgically removed or
treated with definitive radiotherapy.
7. Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the
exception of sorafenib used in first-line therapy regimen as part of induction, consolidation
and/or maintenance).
8. Subject has clinically significant abnormality of coagulation profile, such as disseminated
intravascular coagulation.
9. Subject has had major surgery within 4 weeks prior to the first study dose.
10. Subject has radiation therapy within 4 weeks prior to the first study dose.
11. Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or
subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a
screening echocardiogram (ECHO) performed within 1 month prior to study entry results
in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
12. Subject with mean QTcF > 450 ms at Screening based on central reading.
13. Subject with Long corrected QT interval (QTc) Syndrome at Screening.
14. Subject with hypokalemia and hypomagnesemia at Screening (defined as values below
lower limit of normal [LLN]).
15. Subject requires treatment with concomitant drugs that are strong inducers of CYP3A.
16. Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of
P-gp or substrates of MATE1 with the exception of drugs that are considered absolutely
essential for the care of the subject.
17. Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR
receptors or sigma nonspecific receptor with the exception of drugs that are considered
absolutely essential for the care of the subject.
18. Subject has an active uncontrolled infection.
19. Subject is known to have human immunodeficiency virus infection.
20. Subject has active hepatitis B or C or other active hepatic disorder.
21. Subject has any condition which, in the investigator’s opinion, makes the subject
unsuitable for study participation.
22. Subject has active clinically significant GVHD or is on treatment with systemic
corticosteroids for GVHD.
Waivers to the exclusion criteria will NOT be allowed.
Subject will be excluded from participation if any of the following apply:
1. Subject was diagnosed as acute promyelocytic leukemia.
2. Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
3. Subject has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
4. Subject is in second or later hematologic relapse or has received salvage therapy for
refractory disease.
5. Subject has clinically active central nervous system leukemia.
6. Subject has been diagnosed with another malignancy, unless disease-free for at least
5 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study
if definitive treatment for the condition has been completed. Subjects with organ-confined
prostate cancer with no evidence of recurrent or progressive disease are eligible if
hormonal therapy has been initiated or the malignancy has been surgically removed or
treated with definitive radiotherapy.
7. Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the
exception of sorafenib used in first-line therapy regimen as part of induction, consolidation
and/or maintenance).
8. Subject has clinically significant abnormality of coagulation profile, such as disseminated
intravascular coagulation.
9. Subject has had major surgery within 4 weeks prior to the first study dose.
10. Subject has radiation therapy within 4 weeks prior to the first study dose.
11. Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or
subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a
screening echocardiogram (ECHO) performed within 1 month prior to study entry results
in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
12. Subject with mean QTcF > 450 ms at Screening based on central reading.
13. Subject with Long corrected QT interval (QTc) Syndrome at Screening.
14. Subject with hypokalemia and hypomagnesemia at Screening (defined as values below
lower limit of normal [LLN]).
15. Subject requires treatment with concomitant drugs that are strong inducers of CYP3A.
16. Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of
P-gp or substrates of MATE1 with the exception of drugs that are considered absolutely
essential for the care of the subject.
17. Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR
receptors or sigma nonspecific receptor with the exception of drugs that are considered
absolutely essential for the care of the subject.
18. Subject has an active uncontrolled infection.
19. Subject is known to have human immunodeficiency virus infection.
20. Subject has active hepatitis B or C or other active hepatic disorder.
21. Subject has any condition which, in the investigator’s opinion, makes the subject
unsuitable for study participation.
22. Subject has active clinically significant GVHD or is on treatment with systemic
corticosteroids for GVHD.
Waivers to the exclusion criteria will NOT be allowed.
The Estimated Number of Participants
-
Taiwan
38 participants
-
Global
369 participants
