Extension Study to Evaluate Long-Term Effects of Luspatercept in Patients With Myelodysplastic Syndromes (MDS) (A536-05/MK-6143-003)

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