A Phase 2, Open Label, Ascending Dose Study of ACE-536 for the Treatment of Anemia in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)
A Phase 2, Open Label, Ascending Dose Study of ACE-536 for the Treatment of Anemia in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)
The purpose of this study is to evaluate the effects of luspatercept (MK-6143, formerly called ACE-536) on anemia in patients with low or intermediate-1 risk myelodysplastic syndrome (MDS). There is no primary hypothesis in this study.
Key Inclusion Criteria:
Documented diagnosis of idiopathic/de novo myelodysplastic syndrome (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), according to WHO criteria (white blood count, 13,000/uL), that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening
Anemia defined as:
Serum erythropoietin levels and prior erythropoiesis-stimulating agent (ESA) treatment:
Dose escalation cohorts and expansion cohort 1 patients: Serum erythropoietin level >500 U/L, OR, if ≤500 U/L, patient is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable
Expansion cohort 2 patients: If patient is RS+ (defined as having ≥15% ring sideroblasts in the bone marrow), no prior ESA treatment and serum erythropoietin level ≤ 200 U/L. If a patient is RS- (defined as having <15% ring sideroblasts in the bone marrow), prior ESA treatment and any serum erythropoietin level is allowed
No alternative treatment options, per applicable MDS guidelines, are available and/or appropriate for the patient, at the discretion of the investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
Adequate renal (creatinine ≤2 x upper limit of normal [ULN]) and hepatic (total bilirubin <2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x ULN) function
Adequate transferrin saturation (≥15%), ferritin (≥ 50 µg/L), folate (≥4.5 nmol/L [≥2.0 µg/L]) and vitamin B12 (≥148 pmol/L [≥ 200 pg/mL]) during screening (supplementation and retest during screening is acceptable)
Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of luspatercept. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential while participating in the study and for 12 weeks following the last dose of luspatercept, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of luspatercept
Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements
Patients understand and are able to provide written informed consent
Key Exclusion Criteria:
Prior treatment with azacitidine or decitabine
Treatment within 28 days prior to Cycle 1 Day 1 with:
Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1
Treatment with another investigational drug or device, or approved therapy for investigational use ≤28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer
Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1
Platelet count <30 x 109/L.
Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1
History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months prior to Cycle 1 Day 1
Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
Any malignancy other than MDS which has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy or surgery, within the last year prior to Cycle 1 Day 1
Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg
Pregnant or lactating females
History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study
Transfusion event within 7 days prior to Cycle 1 Day 1
Prior treatment with sotatercept (MK-7962, formerly called ACE-011) or luspatercept.
Secondary MDS