luspatercept (drug to treat anemia) in patients to treat anemia associated with myelodysplastic syndromes (MDS-RS) and beta-thalassemia (Beta-Thal) in India

Phase 4

Conditions: Health Condition 1: D758- Other specified diseases of bloodand blood-forming organs

Registration Number: CTRI/2023/03/050272

Lead Sponsor: BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

Beta-Thalassemia

More than 18 years of age at the time of signing the informed consent form

Documented diagnosis of ß-thalassemia or Hemoglobin E/ß-thalassemia

Regularly transfused, defined as 6-20 Red Blood Cell (RBC) units in the 24 weeks prior to randomization and no transfusion-free period for more than 35 days during that period.

Sites who prescribe transfusions and have the transfusion records only in volumes should use for conversion of volume to units the below criteria, in order to obtain number of units within the last 24 weeks to assess the eligibility: 1 unit in this protocol refers to a quantity of packed RBCs approximately 200-350 mL. 1. sites who use transfusion bags within this range, or more than equal to 350 mL, the conversion in units should be done by dividing the volume transfused to the patient by 350 mL, 2. sites who use transfusion bags less than 200 mL, the conversion in units should be done by dividing the volume transfused to the patient by 200 mL.

Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

MDS

More than 18 years of age at the time of signing the informed consent form

Subject had documented diagnosis of MDS according to WHO/FAB (2016) classification that met IPSS-R classification of very low-, low-, or intermediate-risk disease, and the following:

Ring sideroblasts (RS) more than equal to 15% of erythroid precursors in bone marrow. If the SF3B1 mutation is present, RS more than equal to 5% will be included.

Less than 5% blasts in bone marrow and less than 1% peripheral blood blasts

Peripheral blood white blood cell (WBC) count less than 13,000/µL

Subject was refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following:

Refractory to prior ESA treatment: Documentation of nonresponse or response that was no longer maintained to prior ESA-containing regimen, either as a single agent or in combination (e.g., with G-CSF). The ESA regimen must have been either:

Recombinant human erythropoietin more than equal to 40,000 IU/week for at least 8 doses or equivalent; or 1050 mg/kg/week for at least 8 doses or equivalent

Darbepoetin- darbepoetin alpha more than equal to 240 µg every week for at least 12 weeks or equivalent

Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA-containing regimen, either as a single agent or in combination (e.g., with G-CSF), at any time after introduction due to intolerance or an AE

ESA ineligible: Low chance of response to ESA based on endogenous serum EPO level more than 200 U/L for subjects not previously treated with ESAs

If the patient was previously treated with ESAs or G-CSF/granulocyte-macrophage colony-stimulating factor (GM-CSF), both agents must have been discontinued more than equal to 4 weeks prior to the date of randomization

Required RBC transfusions, as documented by the following criteria:

Average transfusion requirement of more than equal to 2 units/8 weeks of packed RBCs (pRBCs) confirmed for a minimum of 16 weeks immediately preceding Luspatercept treatment

Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been less than equal to 9.0 g/dL with symptoms of anemia or (less than equal to 7 g/dl in absence of symptoms) in order for the transfusion to be c

Exclusion Criteria

Beta-Thalassemia

A diagnosis of Haemoglobin S/ß-thalassemia or alpha (a)-thalassemia (e.g., Haemoglobin H).

Deep Vein Thrombosis (DVT) or stroke requiring medical intervention more than equal to 24 weeks prior to randomization.

Use of chronic anticoagulant therapy is excluded unless the treatment stopped at least 28 days prior to randomization. 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.

Platelet count more than 1000 x 109/L

Poorly controlled diabetes mellitus within 24 weeks prior to randomization as defined by short term (e.g., hyperosmolar or ketoacidotic crisis) and/or history of diabetic cardiovascular complications (e.g., stroke or myocardial infarction).

Pregnant or lactating females.

Uncontrolled hypertension. Controlled hypertension for this protocol is considered less than equal to Grade 1 according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (current active minor version).

Major organ damage, including:

Liver disease with alanine aminotransferase (ALT) more than 3 x the upper limit of normal (ULN) or history of evidence of cirrhosis.

Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of randomization.

Lung disease, including pulmonary fibrosis or pulmonary hypertension which are clinically significant i.e., more than equal to Grade 3 NCI CTCAE version 4.0 (current active minor version).

Creatinine clearance less than 60 mL/min (per Cockcroft-Gault formula).

MDS

MDS associated with del 5q cytogenetic abnormality

Secondary MDS, i.e., MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.

Subject has known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding.

Iron deficiency to be determined by serum ferritin = 15 µg/L and additional testing if clinically indicated (e.g., calculated transferrin saturation [iron/total iron binding capacity = 20%] or bone marrow aspirate stain for iron)

Prior allogeneic or autologous stem cell transplant

Known history of diagnosis of AML

Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure

Subject has uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of = 150 mmHg and/or diastolic blood pressure (DBP) = 100 mmHg despite adequate treatment, or with a history of hypertensive crisis or hypertensive encephalopathy

Absolute neutrophil count (ANC) < 500/µL (0.5 x 109/L)

Platelet count < 50,000/µL (50 x 109/L)

Estimated glomerular filtration rate (eGRF) or creatinine clearance < 40 mL/min/1.73 m2 or creatinine clearance < 40 mL/min.

Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) = 3.0 x upper limit of normal (ULN)

Total bilirubin = 2.0 x ULN.

higher levels are acceptable if these can be attributed to active red blo

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Beta-Thalassemia <br/ ><br>Incidence of treatment related adverse events of grade 3 or higher adverse events: during the treatment period (up to 48 weeks) & during a 9-week follow-up period after the last cycle of study drug in B-Thalassemia. <br/ ><br> <br/ ><br>MDS <br/ ><br>Incidence of treatment related adverse events of grade 3 or higher adverse events: during the treatment period (up to 48 weeks) & during a 6-week follow-up period after the last cycle of study drug in MDS <br/ ><br>Timepoint: screening visit,every 3 weeks (up to 48 weeks) & 9-week follow-up period after the last cycle of study drug in B-Thalassemia. <br/ ><br> <br/ ><br>MDS <br/ ><br>Screening visit, every 3 week (up to 48 weeks) & 6-week follow-up period after the last cycle of study drug in MDS <br/ ><br>

Secondary Outcome Measures