The purpose of this clinical trial is to test how well the drug luspatercept works in improving low blood cell counts in people with clonal cytopenias of uncertain significance (CCUS). The main questions the study seeks to answer include:
* How many patients experience improvements in their low blood counts (red cells, platelets, or white cells) within 24 weeks, based on specific criteria for blood conditions like myelodysplastic syndromes (MDS)? * How long these improvements last before the condition worsens or changes. * The percentage of participants showing improvements at 12, 24, and 48 weeks. * How long it takes for the condition to progress to more severe diseases like myeloid disorders. * How long red blood cell responses last and how quickly these responses are seen. * The average change in hemoglobin levels over 24 weeks. * How many patients need blood transfusions during the study and how soon transfusions are required. * Changes in participants' well-being and energy levels based on a standardized questionnaire. * Monitoring for any side effects, including progression to MDS or leukemia, heart-related issues, or sudden increases in hemoglobin.
Participants will:
* Receive luspatercept as an injection every three weeks. * Visit the clinic every three weeks for treatment and monitoring.
Male or female ≥ 18 years of age.
Documentation of a CCUS diagnosis.
Clonal cytopenia of undetermined significance (CCUS) is defined as clonal hematopoiesis of indeterminate potential (CHIP) detected in the presence of one or more persistent cytopenias that are otherwise unexplained by hematologic or non-hematologic conditions and that do not meet diagnostic criteria for defined myeloid neoplasms. Cytopenia definitions for diagnosis of CCUS include Hb <13 g/dL in males and <12 g/dL in females for anemia, absolute neutrophil count <1.8 ×109/L for leukopenia, and platelets <150 × 109/L for thrombocytopenia.
Patients should harbor somatic mutations of myeloid malignancy-associated genes detected in the blood or bone marrow at a variant allele fraction (VAF) of ≥ 2% (≥4% for X-linked gene mutations in males
Concurrent malignancy requiring active concurrent systemic chemotherapy. Hormonal therapy for malignancy and targeted radiation is allowed. If patients after enrollment, have a clinical need for chemotherapy after achieving response on treatment, subjects deriving clinical benefit can be continued on study after discussion with study PI.
Diagnosis of MDS, AML, MPN or any other myeloid malignancy in the patient's lifetime
Active uncontrolled infection that in the investigators opinion will affect study procedures and/or results
Active uncontrolled hypertension not responding to blood pressure lowering medications which in the investigator's opinion will be harmful for the patient.
Weill Medical College of Cornell University
Lead sponsor
Bristol-Myers Squibb
Collaborator