A Phase 3 study to see the benefit and safety of Luspatercept in comparison with Epoetin Alfa to treat anaemia due to very low, low or intermediate risk Myelodysplastic Syndromes (MDS) in people who have not taken erythropoiesis-stimulating agents (ESA's) before and who require red blood cell transfusions.
- Conditions
- Myelodysplastic syndrome (MDS)MedDRA version: 20.0Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-003190-34-LT
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
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 that meets IPSS R classification 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:
• A transfusion requirement of 2 to 6 pRBCs units/8 weeks 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 (5.6 mmol/L) with symptoms of anemia (or = 7 g/dL [4.3 mmol/L] 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 (6.8 mmol/L) (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 achieved menarche at some point, 2) not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons 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). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
•Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented), or agree to use, and be able to comply with, highly effective contraception 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 abstinence (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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 103
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects fo
1. Subject with the any of the following prior treatments:
•Erythropoiesis-stimulating agents (ESAs)
Subjects may be randomized at the investigator’s discretion contingent on the fact that the subject received no more than 2 doses of epoetin alfa (prior treatment with darbepoetin not acceptable for entry into the study). The last dose of epoetin alfa must be = 8 weeks from the date of randomization. A blood sample to determine the endogenous sEPO level (central laboratory) for stratification must be taken within 5 days of randomization unless a prior screening sample analyzed by the central laboratory demonstrated an endogenous sEPO level = 500 U/L
•Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), within 8 weeks prior to randomization, 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 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,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method