Clinical Trials List
Protocol NumberACE-536-MDS-002
NCT Number(ClinicalTrials.gov Identfier)NCT03682536
2018-09-01 - 2026-10-02
Phase III
Not yet recruiting1
Recruiting4
ICD-9238.7
Neoplasm of uncertain behavior of other lymphatic and hematopoietic tissues
A PHASE 3, OPEN-LABEL, RANDOMIZED STUDY TO COMPARE THE EFFICACY AND SAFETY OF LUSPATERCEPT (ACE-536) VERSUS EPOETIN ALFA FOR THE TREATMENT OF ANEMIA DUE TO IPSS-R VERY LOW, LOW OR INTERMEDIATE RISK MYELODYSPLASTIC SYNDROMES (MDS) IN ESA NAiVE SUBJECTS WHO REQUIRE RED BLOOD CELL TRANSFUSIONS
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Celgene Corporation
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ching Yun Hsieh Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- HSIN-CHEN LIN Division of Hematology & Oncology
- ZHENG-WEI ZHOU Division of Hematology & Oncology
- YU-HSUAN SHIH Division of Hematology & Oncology
- 騰傑林 Division of Hematology & Oncology
- Chieh-Lin Teng Division of Hematology & Oncology
- Tsung -Chih Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 田豐銘 Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- Wen-Chien Chou Division of Others -
- Shang-Ju Wu Division of Hematology & Oncology
- 徐思淳 Division of Others
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Myelodysplastic Syndromes
Objectives
Primary objective:
To evaluate the efficacy of luspatercept on RBC transfusion independence (RBC-TI)
compared to epoetin alfa for the treatment of anemia due to IPSS-R very low, low, or
intermediate risk MDS in ESA naïve subjects who require RBC transfusions
Key secondary objectives:
To assess the safety and efficacy of luspatercept compared to epoetin alfa
To assess health-related quality-of-life (HRQoL) and anemia outcome measures (ie,
European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire [EORTC QLQ-C30] and the Functional Assessment of Cancer
Therapy - Anemia [FACT-An] questionnaire) for subjects treated with luspatercept
compared to epoetin alfa
Test Drug
Luspatercept; Epoetin alfa
Active Ingredient
Epoetin alfa
Luspatercept (ACE-536)
Luspatercept (ACE-536)
Dosage Form
injection
Dosage
25mg
75mg
2000IU
4000IU
6000IU
20000IU
30000IU
40000IU
75mg
2000IU
4000IU
6000IU
20000IU
30000IU
40000IU
Endpoints
Key Efficacy Assessments
Efficacy assessments include the collection of transfusion data (eg, RBC transfusions),
assessment of hematological parameters (eg, hemoglobin, platelet count, neutrophils) and central
cytomorphology and cytogenetics review of bone marrow aspirate and peripheral blood for MDS
disease assessment.
Response assessment according to the International Working Group (IWG) criteria (Cheson,
2006) is to be performed at the 24-Week MDS Disease Assessment Visit (ie, Day 169) and every
24 weeks (ie, 168 days) thereafter.
For a detailed description of efficacy assessments please refer to Section 6.4.
Key Safety Assessments
Safety assessments include hematology (complete blood count [CBC] with differential) and
serum chemistry analyses, recording of adverse events, physical exam, vital signs and
electrocardiograms (ECGs) (if clinically indicated). In addition, subjects will be monitored for
progression to AML and other malignancies/pre-malignancies.
Efficacy assessments include the collection of transfusion data (eg, RBC transfusions),
assessment of hematological parameters (eg, hemoglobin, platelet count, neutrophils) and central
cytomorphology and cytogenetics review of bone marrow aspirate and peripheral blood for MDS
disease assessment.
Response assessment according to the International Working Group (IWG) criteria (Cheson,
2006) is to be performed at the 24-Week MDS Disease Assessment Visit (ie, Day 169) and every
24 weeks (ie, 168 days) thereafter.
For a detailed description of efficacy assessments please refer to Section 6.4.
Key Safety Assessments
Safety assessments include hematology (complete blood count [CBC] with differential) and
serum chemistry analyses, recording of adverse events, physical exam, vital signs and
electrocardiograms (ECGs) (if clinically indicated). In addition, subjects will be monitored for
progression to AML and other malignancies/pre-malignancies.
Inclution Criteria
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
4. Subject has a documented diagnosis of MDS according to WHO 2016 classification
(Section 6.1.1, Appendix B) that meets IPSS-R classification (Greenberg, 2012) of very
low, low, or intermediate risk disease, and:
< 5% blasts in bone marrow.
5. Subject has an endogenous serum erythropoietin (sEPO) level of < 500 U/L.
6. Subject requires RBC transfusions, as documented by the following criteria
(Section 6.1.2):
Average transfusion requirement of 2 - 6 units/8 weeks of pRBCs confirmed for a
minimum of 8 weeks immediately preceding randomization.
Hemoglobin levels at the time of or within 7 days prior to administration of a
RBC transfusion must have been ≤ 9.0 g/dL with symptoms of anemia (or
≤ 7 g/dL in the absence of symptoms) in order for the transfusion to be counted
towards meeting eligibility criteria. Red blood cell transfusions administered
when Hgb levels were > 9.0 g/dL (or > 7 g/dL in the absence of symptoms) and/or
RBC transfusions administered for elective surgery, infections or bleeding events
will not qualify as a required transfusion for the purpose of meeting eligibility
criteria or stratification.
The hemoglobin level after the last RBC transfusion prior to randomization must
be < 11.0 g/dL (centrally or locally analyzed).
7. Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
8. Females of childbearing potential (FCBP), defined as a sexually mature woman who:
1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been
naturallypostmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time
in the preceding 24 consecutive months), must:
Have two negative pregnancy tests as verified by the investigator prior to starting
study therapy (unless the screening pregnancy test was done within 72 hours of
W1D1). Refer to Section 6.1.14 for additional details. She must agree to ongoing
pregnancy testing during the course of the study, and after end of study treatment.
If sexually active, agree to use, and be able to comply with, highly effective
contraception1 without interruption, 5 weeks prior to starting investigational product,
during the study therapy (including dose interruptions), and for 12 weeks after
discontinuation of study therapy.
9. Male subjects must:
Practice true abstinence2
(which must be reviewed prior to each IP administration or
on a monthly basis [eg, in the event of dose delays]) or agree to use a condom (latex
or non-latex, but not made out of natural [animal] membrane) during sexual contact
with a pregnant female or a female of childbearing potential while participating in the
study, during dose interruptions and for at least 12 weeks following investigational
product discontinuation, even if he has undergone a successful vasectomy.
Subjects must satisfy the following criteria to be randomized in the study:
1. Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
4. Subject has a documented diagnosis of MDS according to WHO 2016 classification
(Section 6.1.1, Appendix B) that meets IPSS-R classification (Greenberg, 2012) of very
low, low, or intermediate risk disease, and:
< 5% blasts in bone marrow.
5. Subject has an endogenous serum erythropoietin (sEPO) level of < 500 U/L.
6. Subject requires RBC transfusions, as documented by the following criteria
(Section 6.1.2):
Average transfusion requirement of 2 - 6 units/8 weeks of pRBCs confirmed for a
minimum of 8 weeks immediately preceding randomization.
Hemoglobin levels at the time of or within 7 days prior to administration of a
RBC transfusion must have been ≤ 9.0 g/dL with symptoms of anemia (or
≤ 7 g/dL in the absence of symptoms) in order for the transfusion to be counted
towards meeting eligibility criteria. Red blood cell transfusions administered
when Hgb levels were > 9.0 g/dL (or > 7 g/dL in the absence of symptoms) and/or
RBC transfusions administered for elective surgery, infections or bleeding events
will not qualify as a required transfusion for the purpose of meeting eligibility
criteria or stratification.
The hemoglobin level after the last RBC transfusion prior to randomization must
be < 11.0 g/dL (centrally or locally analyzed).
7. Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
8. Females of childbearing potential (FCBP), defined as a sexually mature woman who:
1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been
naturallypostmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time
in the preceding 24 consecutive months), must:
Have two negative pregnancy tests as verified by the investigator prior to starting
study therapy (unless the screening pregnancy test was done within 72 hours of
W1D1). Refer to Section 6.1.14 for additional details. She must agree to ongoing
pregnancy testing during the course of the study, and after end of study treatment.
If sexually active, agree to use, and be able to comply with, highly effective
contraception1 without interruption, 5 weeks prior to starting investigational product,
during the study therapy (including dose interruptions), and for 12 weeks after
discontinuation of study therapy.
9. Male subjects must:
Practice true abstinence2
(which must be reviewed prior to each IP administration or
on a monthly basis [eg, in the event of dose delays]) or agree to use a condom (latex
or non-latex, but not made out of natural [animal] membrane) during sexual contact
with a pregnant female or a female of childbearing potential while participating in the
study, during dose interruptions and for at least 12 weeks following investigational
product discontinuation, even if he has undergone a successful vasectomy.
Exclusion Criteria
Exclusion Criteria
The presence of any of the following will exclude a subject from randomization (with the
randomization date defined as the date in which the subject is randomized in IRT):
1. Subject with the any of the following prior treatments:
Erythropoiesis-stimulating agents (ESAs)
Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colonystimulating factor (GM-CSF), unless given for treatment of febrile neutropenia
Disease modifying agents (eg, immune-modulatory drug [IMiDs such as
lenalidomide]
Except if the subject received ≤ 1 week of treatment with a disease modifying
agent ≥ 8 weeks from randomization, at the investigator’s discretion.
Hypomethylating agents
Subjects may be randomized at the investigator’s discretion contingent that the
subject received no more than 2 doses of HMA. The last dose must be ≥ 8 weeks
from the date of randomization.
Luspatercept (ACE-536) or sotatercept (ACE-011)
Immunosuppressive therapy for MDS
Hematopoietic cell transplant
2. Subject with MDS associated with del(5q) cytogenetic abnormality or MDS
unclassifiable (MDS-U) according to WHO 2016 classification.
3. Subject with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) according to
WHO 2016 classification (ie, Chronic myelomonocytic leukemia (CMML), Atypical
chronic myeloid leukemia (aCML), BCR-ABL12, Juvenile myelomonocytic leukemia
(JMML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T),
MDS/MPN unclassifiable.
4. Subject with secondary MDS, ie, MDS that is known to have arisen as the result of
chemical injury or treatment with chemotherapy and/or radiation for other diseases.
5. Subject with known clinically significant anemia due to iron, vitamin B12, or folate
deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any
type of known clinically significant bleeding or sequestration. Subject with drug induced
anemia (eg, mycophenolate).
Iron deficiency to be determined by serum ferritin < 100 µg/L and additional testing
if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding
capacity ≤ 20%] or bone marrow aspirate stain for iron).
6. Subject with known history of diagnosis of AML.
7. Subject receiving any of the following treatment within 8 weeks prior to randomization:
Anticancer cytotoxic chemotherapeutic agent or treatment
Systemic corticosteroid, except for subjects on a stable or decreasing dose for
≥ 1 week prior to randomization for medical conditions other than MDS
Iron-chelating agents, except for subjects on a stable or decreasing dose for at least
8 weeks prior to randomization
Other RBC hematopoietic growth factors (eg, Interleukin-3)
Androgens, unless to treat hypogonadism
Hydroxyurea
Oral retinoids (except for topical retinoids)
Arsenic trioxide
Interferon and interleukins
Investigational drug or device, or approved therapy for investigational use (if 5 times
the half-life of the previous investigational drug exceeds 8 weeks, then the time of
exclusion should be extended up to 5 times the half-life of the investigational drug)
8. Subject with uncontrolled hypertension, defined as repeated elevations of systolic blood
pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg
despite adequate treatment.
9. Subject with any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) < 500/μL (0.5 x 109
/L)
Platelet count < 50,000/μL (50 x 109
/L)
Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2
(via the 4-variable
modification of diet in renal disease [MDRD] formula)
Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase
(AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase
(ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
Total bilirubin ≥ 2.0 x ULN.
Higher levels are acceptable if these can be attributed to active red blood cell
precursor destruction within the bone marrow (ie, ineffective erythropoiesis) or in
the presence of known history of Gilbert Syndrome.
10. Subject with prior history of malignancies, other than MDS, unless the subject has been
free of the disease for ≥ 5 years. However, subjects with the following
history/concurrent conditions are allowed:
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes,
metastasis [TNM] clinicalstaging system)
11. Subject with major surgery within 8 weeks prior to randomization. Subjects must have
completely recovered from any previous surgery prior to randomization.
12. Subject with history of cerebrovascular accident (including ischemic, embolic, and
hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous
thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism,
arterial thrombosis or other venous thrombosis within 6 months prior to randomization
Note: prior superficial thrombophlebitis is not an exclusion criterion.
13. New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization.
14. Subject with the following cardiac conditions within 6 months prior to randomization:
myocardial infarction, uncontrolled angina, acute decompensated cardiac failure or New
York Heart Association (NYHA) Class III-IV heart failure, or uncontrolled cardiac
arrhythmia as determined by the investigator. Subjects with a known ejection fraction
˂ 35%, confirmed by a local echocardiogram (ECHO) or multi-gated acquisition
(MUGA) scan performed within 6 months prior to randomization.
15. Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy, and/or other treatment).
16. Subject with known human immunodeficiency virus (HIV), known evidence of active
infectious Hepatitis B, and/or known evidence of active Hepatitis C.
17. Subject with history of severe allergic or anaphylactic reactions or hypersensitivity to
recombinant proteins or excipients in luspatercept (see Investigator’s Brochure).
18. Subject with known hypersensitivity to the active substance or to any of the excipients in
epoetin alfa.
19. Subjects with history of pure red cell aplasia (PRCA) and/or antibody against
erythropoietin.
20. Pregnant or breastfeeding females.
21. Subject has any significant medical condition, laboratory abnormality, psychiatric illness,
or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that
would prevent the subject from participating in the study.
22. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.
23. Subject has any condition or receives concomitant medication that confounds the ability
to interpret data from the study
The presence of any of the following will exclude a subject from randomization (with the
randomization date defined as the date in which the subject is randomized in IRT):
1. Subject with the any of the following prior treatments:
Erythropoiesis-stimulating agents (ESAs)
Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colonystimulating factor (GM-CSF), unless given for treatment of febrile neutropenia
Disease modifying agents (eg, immune-modulatory drug [IMiDs such as
lenalidomide]
Except if the subject received ≤ 1 week of treatment with a disease modifying
agent ≥ 8 weeks from randomization, at the investigator’s discretion.
Hypomethylating agents
Subjects may be randomized at the investigator’s discretion contingent that the
subject received no more than 2 doses of HMA. The last dose must be ≥ 8 weeks
from the date of randomization.
Luspatercept (ACE-536) or sotatercept (ACE-011)
Immunosuppressive therapy for MDS
Hematopoietic cell transplant
2. Subject with MDS associated with del(5q) cytogenetic abnormality or MDS
unclassifiable (MDS-U) according to WHO 2016 classification.
3. Subject with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) according to
WHO 2016 classification (ie, Chronic myelomonocytic leukemia (CMML), Atypical
chronic myeloid leukemia (aCML), BCR-ABL12, Juvenile myelomonocytic leukemia
(JMML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T),
MDS/MPN unclassifiable.
4. Subject with secondary MDS, ie, MDS that is known to have arisen as the result of
chemical injury or treatment with chemotherapy and/or radiation for other diseases.
5. Subject with known clinically significant anemia due to iron, vitamin B12, or folate
deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any
type of known clinically significant bleeding or sequestration. Subject with drug induced
anemia (eg, mycophenolate).
Iron deficiency to be determined by serum ferritin < 100 µg/L and additional testing
if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding
capacity ≤ 20%] or bone marrow aspirate stain for iron).
6. Subject with known history of diagnosis of AML.
7. Subject receiving any of the following treatment within 8 weeks prior to randomization:
Anticancer cytotoxic chemotherapeutic agent or treatment
Systemic corticosteroid, except for subjects on a stable or decreasing dose for
≥ 1 week prior to randomization for medical conditions other than MDS
Iron-chelating agents, except for subjects on a stable or decreasing dose for at least
8 weeks prior to randomization
Other RBC hematopoietic growth factors (eg, Interleukin-3)
Androgens, unless to treat hypogonadism
Hydroxyurea
Oral retinoids (except for topical retinoids)
Arsenic trioxide
Interferon and interleukins
Investigational drug or device, or approved therapy for investigational use (if 5 times
the half-life of the previous investigational drug exceeds 8 weeks, then the time of
exclusion should be extended up to 5 times the half-life of the investigational drug)
8. Subject with uncontrolled hypertension, defined as repeated elevations of systolic blood
pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg
despite adequate treatment.
9. Subject with any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) < 500/μL (0.5 x 109
/L)
Platelet count < 50,000/μL (50 x 109
/L)
Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2
(via the 4-variable
modification of diet in renal disease [MDRD] formula)
Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase
(AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase
(ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
Total bilirubin ≥ 2.0 x ULN.
Higher levels are acceptable if these can be attributed to active red blood cell
precursor destruction within the bone marrow (ie, ineffective erythropoiesis) or in
the presence of known history of Gilbert Syndrome.
10. Subject with prior history of malignancies, other than MDS, unless the subject has been
free of the disease for ≥ 5 years. However, subjects with the following
history/concurrent conditions are allowed:
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes,
metastasis [TNM] clinicalstaging system)
11. Subject with major surgery within 8 weeks prior to randomization. Subjects must have
completely recovered from any previous surgery prior to randomization.
12. Subject with history of cerebrovascular accident (including ischemic, embolic, and
hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous
thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism,
arterial thrombosis or other venous thrombosis within 6 months prior to randomization
Note: prior superficial thrombophlebitis is not an exclusion criterion.
13. New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization.
14. Subject with the following cardiac conditions within 6 months prior to randomization:
myocardial infarction, uncontrolled angina, acute decompensated cardiac failure or New
York Heart Association (NYHA) Class III-IV heart failure, or uncontrolled cardiac
arrhythmia as determined by the investigator. Subjects with a known ejection fraction
˂ 35%, confirmed by a local echocardiogram (ECHO) or multi-gated acquisition
(MUGA) scan performed within 6 months prior to randomization.
15. Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy, and/or other treatment).
16. Subject with known human immunodeficiency virus (HIV), known evidence of active
infectious Hepatitis B, and/or known evidence of active Hepatitis C.
17. Subject with history of severe allergic or anaphylactic reactions or hypersensitivity to
recombinant proteins or excipients in luspatercept (see Investigator’s Brochure).
18. Subject with known hypersensitivity to the active substance or to any of the excipients in
epoetin alfa.
19. Subjects with history of pure red cell aplasia (PRCA) and/or antibody against
erythropoietin.
20. Pregnant or breastfeeding females.
21. Subject has any significant medical condition, laboratory abnormality, psychiatric illness,
or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that
would prevent the subject from participating in the study.
22. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.
23. Subject has any condition or receives concomitant medication that confounds the ability
to interpret data from the study
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
350 participants
