Anemia due to MDS with del5q with IPSS-R very low, low, or intermediate risk MDS and a bone marrow blast count of < 5% , Refractory or intolerant to, or ineligible for, prior ESA treatment and for prior lenalidomide treatment and who require RBC transfusions. MedDRA version: 20.0 Level: LLT Classification code 10028532 Term: Myelodysplasia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Reblozyl
Product Name: Luspatercept
Product Code: [ACE-536]
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Luspatercept
CAS Number: 1373715-00-4
Current Sponso
Sponsors
ASSOCIAZIONE QOL-ONE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be included 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. Documented diagnosis of MDS with del5q according to 2018 WHO classification 4. IPSS-R classification (Greenberg, 2012) of very low, low, or intermediate risk disease, and: • 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria. • no consecutive 56-day period that was RBC transfusion-free during the 16 weeks immediately preceding screening 8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 9. Females of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (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 C1D1). Refer to Section 6.1 for additional details. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. • If sexually active, 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. 10. Male subjects must: • Agree to use a condom, defined as a male latex condom or non latex condom not made out of natural (animal) membrane (for example, polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dos
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from study entry: 1. P53 mutation at screening 2. Prior therapy with disease modifying agents for underlying MDS disease (hypomethylating agents) • subjects who previously received HMA may be enrolled at the investigator’s discretion contingent that the subject received no more than 1 dose of HMA). The last dose must be = 5 weeks from the date of screening. 3. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011) 4. 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 Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding 6. Prior allogeneic or autologous stem cell transplant 7. Known history of diagnosis of AML 8. Use of any of the following within 5 weeks prior to study entry: • anticancer cytotoxic chemotherapeutic agent or treatment • corticosteroid, except for subjects on a stable or decreasing dose for = 1 week prior to study entry 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 screening • other RBC hematopoietic growth factors • investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half- life prior to screening or within 5 weeks, whichever is longer is excluded. 9. Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) = 100 mmHg despite adequate treatment. 10. Estimated glomerular filtration rate (eGFR) or creatinine clearance < 40 mL/min. 11. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase or alanine aminotransferase/serum glutamic pyruvic transaminase = 3.0 x upper limit of normal (ULN) 12. 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. • subjects are excluded if there is evidence of autoimmune hemolytic anemia 13. Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) 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] clinical staging system)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of luspatercept on RBC TI (lack of transfusions for 8 consecutive weeks within the first 24 weeks) in subjects with MDS with del5q with IPSS-R very low, low, or intermediate risk and < 5% bone marrow blasts, resistant/refractory/intolerant to lenalidomide and RBC TD.;Secondary Objective: To evaluate: othe safety and tolerability of luspatercept oRBC-TI at 48 weeks and end of study othe duration of RBC-TI othe reduction in RBC transfusions othe increase in hemoglobin othe change in quality of life scores (ie, QOL-E and HM-PRO) othe change in serum ferritin othe change in iron chelation therapy use othe time to RBC TI.;Primary end point(s): RBC Transfusion Independence (for 8 weeks in the first 24 weeks);Timepoint(s) of evaluation of this end point: From study entry to week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability of Luspatercept RBC-TI at 48 weeks and end of the study Duration of RBC-TI Reduction in RBC transfusions Increase in hemoglobin Change in quality of life scores (ie. QOL-E and HM-PRO) Change in Serum Ferritin Change in iron chelation therapy use Time to RBC TI;Timepoint(s) of evaluation of this end point: From study entry to end of study From study entry to week 48 and month 24 From study entry to month 24 Study entry through week 24 Study entry through month 24 Study entry through month 24 Study entry through month 24 Study entry through month 24 From study entry to week 24 | — |
Countries
Italy
Contacts
Public ContactTrial Office
ASSOCIAZIONE QOL-ONE
Outcome results
None listed