Clinical trial NCT05891249: A Study to Evaluate the Safety and Effectiveness of Luspatercept for the Treatment of Transfusion-dependent (TD) Anemia Associated With Myelodysplastic Syndromes (MDS) & Beta-thalassemia (β-Thal) in India
Official title: A Phase 4 Study to Evaluate Safety and Effectiveness of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) With Ring Sideroblasts Who Require Red Blood Cell Transfusions in Participants Who Have Had Unsatisfactory Response to or Are Ineligible to Erythropoietin Based Therapy and in Participants With Transfusion Dependent Anemia Due to Beta-Thalassemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Anemia
Keywords: Luspatercept
ACE-536
Transfusion dependent
Beta-thalassemia
Myelodysplastic syndromes with ring sideroblasts
Anemia
Hemoglobinopathies
Hematologic diseases
Bone marrow diseases
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2023-06-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of luspatercept in participants who require regular blood cell transfusions due to b-thalassemia and myelodysplastic syndromes in India


Eligibility criteria: Inclusion Criteria:

β-Thalassemia Cohort

* Documented diagnosis of β-thalassemia or hemoglobin (Hb E/β-thalassemia). (β-thalassemia with mutation and/or multiplication of alpha \[α\] globin is allowed).
* Regularly transfused, defined as 6 RBC units to 20 RBC units in the 24 weeks prior to enrollment and no transfusion-free period for \> 35 days during that period.

MDS-RS Cohort

- Participant has documented diagnosis of MDS according to World Health Organization (WHO) (2016)/French-American-British FAB classification that meets revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease and the following criteria: i) RS ≥ 15% of erythroid precursors in bone marrow. If the SF3B1 mutation is present, RS ≥ 5% will be included.

ii) Less than 5% blasts in bone marrow and \< 1% peripheral blood blasts. iii) Peripheral blood white blood cell (WBC) count \< 13,000/ microliters (μL).

* If the participant was previously treated with erythropoiesis-stimulating agents (ESAs) or granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), both agents must have been discontinued ≥ 4 weeks prior to the date of enrollment.

Exclusion Criteria:

β-Thalassemia Cohort

* A diagnosis of Hb S/β-thalassemia or α-thalassemia (for exampe, Hemoglobin H).
* Deep vein thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to enrollment.
* Use of chronic anticoagulant therapy is excluded unless the treatment stopped at least 28 days prior to enrollment. Anticoagulant therapies used for prophylaxis for surgery or high-risk procedures as well as low-molecular-weight (LMW) heparin for superficial venous thrombosis and chronic aspirin are allowed.
* Cytotoxic agents or immunosuppressants or immunomodulatory drugs (IMiDs) ≤ 28 days prior to enrollment (ie, antithymocite globulin or cyclosporine or thalidomide).

MDS-RS Cohort

* MDS associated with del 5q cytogenetic abnormality.
* Secondary MDS, that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
* Participant has known clinically significant anemia due to iron, vitamin B12, or folate deficiencies; autoimmune or hereditary hemolytic anemia; or gastrointestinal bleeding.
* Iron deficiency to be determined by serum ferritin ≤ 15 micrograms per liter (μg/L) and additional testing if clinically indicated (for example, calculated transferrin saturation \[iron/total iron binding capacity ≤ 20%\] or bone marrow aspirate \[BMA\] stain for iron).

Primary outcomes:
measure: β-Thal Cohort: Number of participants with treatment-related adverse events (AEs) of grade 3 or higher
timeFrame: Up to 57 weeks
measure: MDS-Ring Sideroblasts (RS) Cohort: Number of participants with treatment-related AEs of grade 3 or higher
timeFrame: Up to 54 weeks
Secondary outcomes:
measure: β-Thal Cohort: Percentage of participants who achieved red blood cell (RBC) transfusion burden reduction (≥ 33% reduction from baseline) with a reduction of at least 2 red cell units compared to the 12-week interval prior to enrollment
timeFrame: Week 13 to week 24
measure: β-Thal Cohort: Percentage of participants who achieved RBC transfusion burden reduction of at least 33% from baseline during any 12-week interval with a reduction of at least 2 red cell units compared to the 12-week interval prior to enrollment
timeFrame: Up to 57 weeks
measure: MDS-RS Cohort: Percentage of participants who achieved RBC-TI during any consecutive 56-day period
timeFrame: Week 1 to week 24
measure: β-Thal Cohort: Number of participants with treatment-related AEs
timeFrame: Up to 57 weeks
measure: MDS-RS Cohort: Number of participants with treatment-related AEs
timeFrame: Up to 54 weeks
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Local Institution - 0001
state: Delhi
city: Ahmedabad
country: India
facility: Local Institution - 0002
state: Gujarat
city: Kolkata
country: India
facility: Local Institution - 0007
state: West Bengal
city: Assam
country: India
facility: Local Institution - 0005
city: Bangalore
country: India
facility: Local Institution - 0003
city: Chandigarh
country: India
facility: Local Institution - 0004
city: Delhi
country: India
facility: Local Institution - 0010
city: Hyderabad
country: India
facility: Local Institution - 0006
city: Mumbai
country: India
facility: Local Institution - 0008
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: