Luspatercept for Clonal Cytopenias of Uncertain Significance

NCT06788691 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-06027622
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anemia; Leukopenia; Thrombocytopenia; Neutropenia; CCUS Clonal Cytopenia of Undetermined Significance

Outcome Measures

Primary Outcomes (1)

• Number of patients achieving cytopenia responses as defined by HI-E, HI-P, HI-N, mHI-E responses

  Adapted from International Working Group (IWG) 2018 response definition for Myelodysplastic Syndromes

  24 Weeks

Secondary Outcomes (25)

• Duration of cytopenia response

  24 Weeks

• Percentage of Participants Achieving Hematologic Response

  12 Weeks

• Percentage of Participants Achieving Hematologic Response

  24 Weeks

• Percentage of Participants Achieving Hematologic Response

  48 Weeks

• Time to Transformation to Myeloid Disease

  Week 4 (Cycle 1 Week 1) to 24 Weeks

Study Arms (1)

Luspatercept

EXPERIMENTAL

Luspatercept administered at 1 mg/kg IV once every 3 weeks

Drug: Luspatercept

Interventions

Luspatercept DRUG

Administered at 1 mg/kg once every 3 weeks

Luspatercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Clinically significant cytopenias demonstrated in two separate lab draws and defined as cytopenia in any one of the following:
• Anemia: Transfusion dependent (LTD or HTD for Hb \< 9 g/dL based on IWG 2018 criteria). Exception for higher threshold up to 10g/dL for documented moderate or severe angina pectoris, cardiac or pulmonary insufficiency, or ischemic neurologic diseases (per IWG 2018 consensus recommendation).
• Anemia NTD: symptomatic NTD CCUS with Hb \<10 g/dl, symptomatic defined as moderate or worse on ≥ 1 Patient Global Impression of Severity (PGI-S) item (fatigue, shortness of breath, weakness, or dizziness)
• Thrombocytopenia: platelet count less than 30,000 /microL or \< 50,000/microL with documented bleeding events or high risk for bleeding, for example on blood thinners or drugs that inhibit platelet function for other comorbidities.
• Neutropenia: Neutropenia below 750/microl are included in the study. For subjects with neutropenia between 750-1000/microl, subjects should have neutropenia AND a history of serious infection(s).
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Adequate organ function as defined by:
• Direct bilirubin \< 3 x ULN. Indirect hyperbilirubinemia from hemolysis or Gilberts disease are not considered as impaired.
• Estimated Creatinine clearance or GFR \>30 ml/min by institutional standards (for example MDRD or Cockcroft Gault or measured by 24 hour urine clearance).
• ALT and AST \< 3 x ULN
• Females of childbearing potential (FCBP), defined as a sexually mature woman who: 1) has achieved menarche at some point, 2) not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must:

You may not qualify if:

• 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.
• Use of ESA or growth factors within four weeks prior to the start of the study
• Known risk factors for thromboembolism (splenectomy, concomitant use of hormone replacement therapy or recent uncontrolled pulmonary embolism or DVT in the last 6 months). Subjects adequately controlled on anticoagulation are permitted.
• Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods are defined in Section 4.4.
• Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF).

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

RECRUITING

MeSH Terms

Conditions

Anemia; Leukopenia; Thrombocytopenia; Neutropenia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Leukocyte Disorders; Blood Platelet Disorders; Agranulocytosis

Study Officials

• Pinkal Desai, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pinkal Desai, MD

CONTACT

646-962-2700; pid9006@med.cornell.edu

Ameenah Sukkur, BA

CONTACT

646-962-4580; ams4015@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 23, 2025
• Study Start: March 25, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)