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A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MEDALIST)

Primary Purpose

Myelodysplastic Syndromes

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Luspatercept
Placebo
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Luspatercept, Transfusion dependent, Lower risk, Low risk, Myelodysplastic Syndromes, ESA refractory, ESA intolerant, ESA ineligible, ACE-536, Anemia, Ring Sideroblasts, Require Red Blood Cell Transfusions, MEDALIST, MDS, IPSS-R very low/IPSS-R low/IPSS-R intermediate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
  2. Documented diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets IPSS R classification of very low, low, or intermediate risk disease, and:

Ring sideroblast ≥ 15% of erythroid precursors in bone marrow or ≥ 5% (but < 15%) if SF3B1 mutation is present.

  • < 5% blasts in bone marrow
  • Peripheral blood white blood cell (WBC) count < 13,000/µL 3. Requires red blood cell RBC transfusions 4. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 5. Subjects who are refractory/intolerant/ineligible to prior erythropoietin-stimulating agents (ESA) treatment, defined as:
  • Refractory to prior - erythropoietin stimulating agents treatment: documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with granulocyte colony stimulating factor (G-CSF); ESA regimen must have been either recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent OR darbepoetin alpha ≥ 500 μg Q3W for at least 4 doses or equivalent
  • Intolerant to prior ESA treatment: documentation of discontinuation of prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event
  • ESA ineligible: low chance of response to ESA base on endogenous serum erythropoietin level > 200 U/L for subjects not previously treated with ESAs

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Prior therapy with disease modifying agents for underlying MDS disease.
  2. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
  3. MDS associated with del 5q cytogenetic abnormality
  4. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.

  5. 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 less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity less than or equal to 20%] or bone marrow aspirate stain for iron).

  6. Prior allogeneic or autologous stem cell transplant
  7. Known history of diagnosis of acute myeloid leukemia (AML)

  8. Use of any of the following within 5 weeks prior to randomization:

    • anticancer cytotoxic chemotherapeutic agent or treatment
    • corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS
    • iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization
    • other RBC hematopoietic growth factors (eg, Interleukin-3)
    • investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to randomization or within 5 weeks, whichever is longer is excluded.

  9. Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:

    • Basal or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the breast
    • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
  10. Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization

Sites / Locations

  • Stanford Cancer Center
  • Yale University School of Medicine
  • H Lee Moffitt Cancer Center and Research Institute
  • Emory University Hospital
  • Ochsner Medical Institutions
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Karmanos Cancer Institute
  • Montefiore Medical Center Albert Einstein Cancer Center
  • Columbia-Presbyterian Medical Center
  • Gabrail Cancer Center
  • Cleveland Clinic Taussig Cancer Institute
  • Vanderbilt University Medical Center
  • MD Anderson Cancer Center
  • Algemeen Ziekenhuis Klina
  • AZ Sint-Jan AV Brugge
  • UZ Brussels
  • Grand Hopital de Charleroi
  • UZ Gent
  • UZ Leuven
  • Cliniques Universitaires UCL de Mont-Godine
  • Tom Baker Cancer Center
  • Juravinski Cancer Centre
  • Sunnybrook Health Sciences Centre
  • Princess Margaret Hospital
  • CHU d'Angers
  • CHU Hotel
  • CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang
  • Institut Paoli Calmettes
  • CHU de Nice Archet I
  • Hopital Saint Louis
  • Hopital Haut Leveque
  • Centre hospitalier Lyon Sud Hematologie
  • Hopital civil
  • Institut Universitaire du Cancer de Toulouse - Oncopole
  • Hopital Bretonneau
  • Universitatsklinikum Bonn
  • Universitatsklinikum Carl Gustav Carus an der TU Dresden
  • Marien Hospital
  • Universitätsklinikum Düsseldorf
  • Medizinische Hochschule Hannover
  • Klinikum rechts der Isar der Technischen Universität München
  • Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo
  • Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
  • Azienda Ospedaliera Universitaria Careggi
  • Azienda Sanitaria Locale Lecce
  • Fondazione IRCCS Policlinico San Matteo
  • Azienda Ospedaliera Bianchi Melacrino Morelli
  • Fondazione Policlinico Universitario A Gemelli
  • Fondazione PTV Policlinico Tor Vergata
  • VU Medisch Centrum
  • Universitair Medisch Centrum Groningen
  • Spaarne Ziekenhuis
  • Hospital Universitario Cruces
  • Hospital Universitario Vall D hebron
  • Instituto Catalan de Oncologia-Hospital Duran i Reynals
  • Hospital General Universitario Gregorio Marañon
  • Hospital Universitario Central de Asturias
  • Hospital Universitario de Salamanca
  • Hospital Universitario Virgen del Rocio
  • Hospital Universitario La Fe
  • Sahlgrenska Universitetssjukhus
  • Skanes Universitetssjukhus Lund
  • Karolinska University Hospital
  • Akademiska Sjukhuset
  • Cukurova University Medical Faculty Balcali Hospital
  • Ankara University Medical Faculty Cebeci Hospital
  • Istanbul University Cerrahpasa Medical Faculty Hospital
  • Ege Universitesi Tip Fakultesi Hastanesi
  • Aberdeen Royal Infirmary
  • John Radcliffe Hospital
  • St James University Hospital
  • Guys Hospital
  • Kings College Hospital
  • Kings Mill Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Arm - Luspatercept (ACE-536)

Control Arm: Placebo

Arm Description

Starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks

Subcutaneous injection every 3 weeks

Outcomes

Primary Outcome Measures

Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24
RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders.

Secondary Outcome Measures

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24
RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment.
Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48
RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment.
Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48
RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders.
Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period
Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment.
Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period
A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions.
Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions
A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48).
Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score
The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study. It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life.
Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period
Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L.
Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period
Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as: Absolute increase of ≥ 30 X 10^9/L in platelets for participants starting with > 20 X 10^9/L platelets Increase in platelets from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%
Change From Baseline in Mean Serum Ferritin
Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin.
Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT)
Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose.
Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24
Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48
Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)
Percentage of participants progressing to AML throughout the course of the study
Time to Acute Myeloid Leukemia (AML) Progression
Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML.
Overall Survival
Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs). TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)
Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ).
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)
Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)
Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)
Tmax was defined as the observed time to maximum plasma concentration of luspatercept.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax)
Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State
Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state.
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss)
Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule.
Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)
Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent."

Full Information

First Posted
November 10, 2015
Last Updated
November 19, 2021
Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
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1. Study Identification

Unique Protocol Identification Number
NCT02631070
Brief Title
A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes
Acronym
MEDALIST
Official Title
A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo for the Treatment of Anemia Due to the IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
February 9, 2016 (Actual)
Primary Completion Date
June 18, 2019 (Actual)
Study Completion Date
November 26, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in participants with anemia due to the Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate MDS with ring sideroblasts who require red blood cell (RBC) transfusions.
Detailed Description
Anemia is considered to be one of the most prevalent cytopenias in patients who have myelodysplastic syndromes, an umbrella term used to describe disorders relating to the ineffective production of red blood cells, white blood cells, and/or platelets. Ranging in severity from mild (asymptomatic) to severe, anemia can result in patients requiring regular red blood cell (RBC) transfusions, which can lead to further complications from iron overload. The goal of this study is to assess the safety and efficacy of luspatercept versus placebo in anemic patients who are categorized as International Prognostic Scoring System-Revised (IPSS-R) very low, low, or intermediate risk Myelodysplastic syndrome (MDS), have ring sideroblasts present, and require constant RBC transfusions. The design of the study will allow a period of initial randomization of patients into either the luspatercept or placebo arm, followed by a double-blind treatment period, and then an MDS disease assessment visit. For those patients that are determined to be experiencing clinical benefit as judged from the study Investigator by this disease assessment visit, they will be permitted to enter the double-blind Extension Phase of the study. Once patients are discontinued from study treatment, they will enter a post treatment follow-up period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
Luspatercept, Transfusion dependent, Lower risk, Low risk, Myelodysplastic Syndromes, ESA refractory, ESA intolerant, ESA ineligible, ACE-536, Anemia, Ring Sideroblasts, Require Red Blood Cell Transfusions, MEDALIST, MDS, IPSS-R very low/IPSS-R low/IPSS-R intermediate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
229 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental Arm - Luspatercept (ACE-536)
Arm Type
Experimental
Arm Description
Starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks
Arm Title
Control Arm: Placebo
Arm Type
Placebo Comparator
Arm Description
Subcutaneous injection every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Luspatercept
Other Intervention Name(s)
ACE-536
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24
Description
RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders.
Time Frame
From Week 1 through Week 24 of study treatment
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24
Description
RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment.
Time Frame
From Week 1 through Week 24 of study treatment
Title
Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48
Description
RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment.
Time Frame
From Week 1 through Week 48 of study treatment
Title
Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48
Description
RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders.
Time Frame
From Week 1 through Week 48 of study treatment
Title
Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period
Description
Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment.
Time Frame
At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48
Title
Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period
Description
A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions.
Time Frame
Week 1 through 24 or Week 1 Through Week 48
Title
Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions
Description
A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48).
Time Frame
Week 1 though Week 24 and Week 1 through 48
Title
Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Description
Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Time Frame
From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks
Title
Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Description
Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Time Frame
From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks
Title
Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score
Description
The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study. It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life.
Time Frame
Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days.
Title
Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period
Description
Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L.
Time Frame
Week 1 through Week 24 or Week 1 Through Week 48 of study treatment
Title
Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period
Description
Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as: Absolute increase of ≥ 30 X 10^9/L in platelets for participants starting with > 20 X 10^9/L platelets Increase in platelets from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%
Time Frame
Week 1 through Week 24 or Week 1 Through Week 48 of study treatment
Title
Change From Baseline in Mean Serum Ferritin
Description
Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin.
Time Frame
Baseline and Week 9 through Week 24 and Week 33 through Week 48
Title
Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT)
Description
Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose.
Time Frame
Baseline and Week 9 through Week 24 and Week 33 through Week 48 of study treatment
Title
Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Description
Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24
Time Frame
From first dose to Week 24 of study treatment
Title
Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Description
Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48
Time Frame
From first dose to Week 48 of study treatment
Title
Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)
Description
Percentage of participants progressing to AML throughout the course of the study
Time Frame
From randomization to study completion (up to approximately 57 months)
Title
Time to Acute Myeloid Leukemia (AML) Progression
Description
Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML.
Time Frame
From randomization to study completion (up to approximately 57 months)
Title
Overall Survival
Description
Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up.
Time Frame
From randomization to study completion (up to approximately 57 months)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs). TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Time Frame
From date of first dose up to 42 days after the last dose (up to approximately 83 weeks)
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)
Description
Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ).
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)
Description
Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)
Description
Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)
Description
Tmax was defined as the observed time to maximum plasma concentration of luspatercept.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax)
Description
Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State
Description
Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss)
Description
Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule.
Time Frame
Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Title
Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)
Description
Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent."
Time Frame
From randomization to 1 year post first dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Subject is ≥ 18 years of age the time of signing the informed consent form (ICF). Documented diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets IPSS R classification of very low, low, or intermediate risk disease, and: Ring sideroblast ≥ 15% of erythroid precursors in bone marrow or ≥ 5% (but < 15%) if SF3B1 mutation is present. < 5% blasts in bone marrow Peripheral blood white blood cell (WBC) count < 13,000/µL 3. Requires red blood cell RBC transfusions 4. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 5. Subjects who are refractory/intolerant/ineligible to prior erythropoietin-stimulating agents (ESA) treatment, defined as: Refractory to prior - erythropoietin stimulating agents treatment: documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with granulocyte colony stimulating factor (G-CSF); ESA regimen must have been either recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent OR darbepoetin alpha ≥ 500 μg Q3W for at least 4 doses or equivalent Intolerant to prior ESA treatment: documentation of discontinuation of prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event ESA ineligible: low chance of response to ESA base on endogenous serum erythropoietin level > 200 U/L for subjects not previously treated with ESAs Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: Prior therapy with disease modifying agents for underlying MDS disease. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011) MDS associated with del 5q cytogenetic abnormality Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases. 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 less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity less than or equal to 20%] or bone marrow aspirate stain for iron). Prior allogeneic or autologous stem cell transplant Known history of diagnosis of acute myeloid leukemia (AML) Use of any of the following within 5 weeks prior to randomization: anticancer cytotoxic chemotherapeutic agent or treatment corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization other RBC hematopoietic growth factors (eg, Interleukin-3) investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to randomization or within 5 weeks, whichever is longer is excluded. Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed: Basal or squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system) Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rodrigo Ito, MD
Organizational Affiliation
Celgene
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
H Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Ochsner Medical Institutions
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70123
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Montefiore Medical Center Albert Einstein Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Columbia-Presbyterian Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195-0001
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Algemeen Ziekenhuis Klina
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
Facility Name
AZ Sint-Jan AV Brugge
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
UZ Brussels
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Grand Hopital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Cliniques Universitaires UCL de Mont-Godine
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Tom Baker Cancer Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
CHU d'Angers
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
CHU Hotel
City
Grenoble Cedex 09
ZIP/Postal Code
38043
Country
France
Facility Name
CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille cedex
ZIP/Postal Code
13273
Country
France
Facility Name
CHU de Nice Archet I
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hopital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital Haut Leveque
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
Centre hospitalier Lyon Sud Hematologie
City
Pierre-Bénite cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Hopital civil
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Institut Universitaire du Cancer de Toulouse - Oncopole
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Hopital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Universitatsklinikum Carl Gustav Carus an der TU Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Marien Hospital
City
Dusseldorf
ZIP/Postal Code
40479
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Klinikum rechts der Isar der Technischen Universität München
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo
City
Allessandria
ZIP/Postal Code
15100
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Careggi
City
Firenze
ZIP/Postal Code
50121
Country
Italy
Facility Name
Azienda Sanitaria Locale Lecce
City
Lecce
ZIP/Postal Code
73100
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Azienda Ospedaliera Bianchi Melacrino Morelli
City
Reggio, Calabria
ZIP/Postal Code
89100
Country
Italy
Facility Name
Fondazione Policlinico Universitario A Gemelli
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Fondazione PTV Policlinico Tor Vergata
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
VU Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Spaarne Ziekenhuis
City
Hoofddorp
ZIP/Postal Code
2135
Country
Netherlands
Facility Name
Hospital Universitario Cruces
City
Barakaldo
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital Universitario Vall D hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Instituto Catalan de Oncologia-Hospital Duran i Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
ZIP/Postal Code
33011
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Seville
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Sahlgrenska Universitetssjukhus
City
Göteborg
ZIP/Postal Code
SE-41685
Country
Sweden
Facility Name
Skanes Universitetssjukhus Lund
City
Lund
ZIP/Postal Code
222 41
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-17176
Country
Sweden
Facility Name
Akademiska Sjukhuset
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Cukurova University Medical Faculty Balcali Hospital
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Ankara University Medical Faculty Cebeci Hospital
City
Ankara
ZIP/Postal Code
06590
Country
Turkey
Facility Name
Istanbul University Cerrahpasa Medical Faculty Hospital
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Hastanesi
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Headington
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Facility Name
St James University Hospital
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Guys Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Kings Mill Hospital
City
Sutton in Ashfield
ZIP/Postal Code
NG17 4SL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30504333
Citation
Porter J. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.
Results Reference
background
PubMed Identifier
30617198
Citation
Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
Results Reference
background
PubMed Identifier
31914241
Citation
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.
Results Reference
result
PubMed Identifier
32089218
Citation
Komrokji RS. Luspatercept in Myelodysplastic Syndromes: Who and When? Hematol Oncol Clin North Am. 2020 Apr;34(2):393-400. doi: 10.1016/j.hoc.2019.10.004. Epub 2020 Jan 21.
Results Reference
result
PubMed Identifier
30602619
Citation
Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2.
Results Reference
result

Learn more about this trial

A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

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