extension study to evaluate long-term effects of luspatercept in patients with myelodysplastic syndromes (mds) (a536-05/mk-6143-003)

Conditions: Myelodysplastic Syndromes

Summary: this study is an open-label extension study for participants previously enrolled in study mk-6143-001 (formerly called a536-03, clinicaltrials.gov identifier nct01749514), to evaluate the long-term safety and tolerability of luspatercept (mk-6143) in participants with low or intermediate-1 risk mds.

this study is an open-label extension study to evaluate the safety, tolerability, and pharmacodynamic effects of up to 24 months of luspatercept treatment in participants with low or intermediate-1 risk myelodysplastic syndromes previously treated with luspatercept for up to 3 months in mk-6143-001 study (nct01749514). the starting dose level in this study will be 1.0 mg/kg by subcutaneous (sc) injection every 3 weeks. dose titration/modification rules will be followed for individual participants and will be based upon safety and efficacy data collected during the course of treatment.

Eligibility criteria:
inclusion criteria: * completion of the treatment period in the base study mk-6143-001 (clinicaltrials.gov identifier: nct01749514) * adequate birth control measures * patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements * patient understands and is able to provide written informed consent * in addition, patients with treatment interruption (defined as patients who complete their end-of-study visit in mk-6143-001 and cannot directly roll over to mk-6143-003) must also meet the following criteria: * documented diagnosis of idiopathic/de novo mds or non-proliferative chronic myelomonocytic leukemia (cmml) according to the world health organization (who) criteria 16 (white blood count (wbc) \< 13,000/μl) 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: * mean hemoglobin concentration \< 10.0 g/dl of 2 measurements (one performed within one day prior to cycle 1 day 1 and the other performed 7-28 days prior to cycle 1 day 1), for non-transfusion dependent (ntd) patients (defined as having received ˂ 4 units of red blood cells (rbcs) within 8 weeks prior to cycle 1 day 1), or * transfusion dependent (td), defined as having received ≥ 4 units of rbcs within 8 weeks prior to cycle 1 day 1 * platelet count ≥ 30 x 109/l * eastern cooperative oncology group (ecog) performance status of 0, 1, or 2 (if related to anemia) * adequate renal (creatinine ≤ 2.0 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 exclusion criteria: * discontinuation/withdrawal from the base study a536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication \[e.g. azacitidine\], medical reason or adverse event (ae), hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period * prior treatment with azacitidine or decitabine * treatment within 28 days prior to cycle 1 day 1 with: * an erythropoiesis-stimulating agent (esa), * granulocyte colony-stimulating factor (g-csf) and granulocyte-macrophage colony stimulating factor (gm-csf), * lenalidomide * iron chelation therapy if initiated within 56 days prior to cycle 1 day 1 * treatment with another investigational drug (including sotatercept \[ace-011\]) or device, or approved therapy for investigational use ≤ 28 days prior to cycle 1 day 1, or if the half-life of the previous investigational 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 * known positive for human immunodeficiency virus (hiv), active infectious hepatitis b (hbv) or active infectious hepatitis c (hcv) * uncontrolled hypertension defined as systolic blood pressure (sbp) ≥ 150 mm hg or diastolic blood pressure (dbp) ≥ 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