A Pilot, Open-Label Study of Luspatercept for Patients With Lower Risk Myelodysplastic Syndromes (MDS)

Objectives:

Primary Objectives:

• To assess the clinical activity and safety of luspatercept in patients with transfusion independent lower risk MDS
• To assess the clinical activity and safety of luspatercept in patients with transfusion dependent lower risk MDS
• To study the effects on hematopoeisis of luspatercept in patients treated on this study

Secondary Objectives:

• To assess the duration of response of patients with treated with luspatercept in this study
• To assess the overall survival and time to transformation of patients with treated with luspatercept in this study
• To assess transfusion free survival period in patients that were transfusion independent treated with luspatercept in this study
• To measure trends in neutrophil and platelet counts in patients treated in this study

Inclusion criteria

• Age ≥ 18 years; as MDS there is no significant experience with luspatercept in pediatric patients
• Cohorts #1 and #2: Diagnosis of MDS according to WHO 2023 criteria (5) and with low or int-1 risk by IPSS or a score of ≤ 3.5 by IPSS-R.(3, 22)
• Cohort #2: Patient defined as transfusion dependent by documentation of receiving at least 2 units of packed red blood cells (PRBCs) for a hemoglobin of less than 8.0 g/dL during an 8-week period prior to study enrollment.
• Cohort #1: Patients with symptomatic anemia that are transfusion independent defined as not requiring a transfusion for a hemoglobin of less than 8.0 g/dL during an 8-week period prior to study enrollment.
• MDS patients with either a platelet count of ≤100 K/uL and/or ANC of ≤1.8 K/uL
• Patient must have signed an informed consent and is willing to participate in the study.
• Adequate hepatic function with total bilirubin ≤3 x ULN, AST or ALT ≤3xULN.
• Serum creatinine clearance ≥40mL/min and no end/stage renal disease (using Cockcroft-Gault).
• ECOG performance status </=2.

Exclusion criteria

• Active infection not adequately responding to appropriate antibiotics.
• Prior treatment with luspatercept or sotarcetept
• Female patients who are pregnant or lactating.
• Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months.
• Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
• History of an active malignancy within the past 2 years prior to study entry, with the exception of: a. Adequately treated in situ carcinoma of the cervix uteri b. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin or any other malignancy with a life expectancy of more than 2 years.
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment).