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Trial record 1 of 3 for:    MEDALIST
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A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MEDALIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02631070
Recruitment Status : Active, not recruiting
First Posted : December 15, 2015
Results First Posted : May 22, 2020
Last Update Posted : May 22, 2020
Sponsor:
Collaborator:
Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Celgene

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.


Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Luspatercept Other: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 229 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : February 9, 2016
Actual Primary Completion Date : November 21, 2017
Estimated Study Completion Date : November 5, 2020


Arm Intervention/treatment
Experimental: Experimental Arm - Luspatercept (ACE-536)
Starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks
Drug: Luspatercept
Other Name: ACE-536

Placebo Comparator: Control Arm: Placebo
Subcutaneous injection every 3 weeks
Other: Placebo



Primary Outcome Measures :
  1. Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) of ≥ 8 Weeks From Week 1 Through Week 24 [ Time Frame: Week 1 through Week 24 ]
    RBC-TI response was defined as the absence of any 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 primary phase of the treatment period (first 24 weeks of double-blind 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 :
  1. Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence of ≥ 12 Weeks From Week 1 Through 24 and Week 1 Through Week 48 [ Time Frame: Week 1 to through Week 24 and Week 1 through 48 ]
    Response was defined as the absence of any 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 Primary Phase of the Treatment Period (first 24 weeks of double-blind treatment) or during Week 1 to Week 48. Participants who discontinued the Primary Phase of the Treatment Period or from the study prior to Week 48 respectively, without achieving at least 84 consecutive days of RBC-TI were counted as non-responders.

  2. Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) of ≥ 8 Weeks From Week 1 Through Week 48 [ Time Frame: Week 1 through Week 48 ]
    RBC-TI response was defined as the absence of any 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.

  3. Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period [ Time Frame: Baseline (16 weeks prior to first dose of study drug), Weeks 9 to 24 and Weeks 33 to 48 ]
    Mean change in total number of RBC units transfused over a fixed 16-week period (Week 9-24, Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first IP date.

  4. Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period From Week 1 Through Week 48 [ Time Frame: Week 1 through 24 and Week 1 Through Week 48 ]
    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.

  5. 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 RBC Transfusions [ Time Frame: Week 1 though Week 24 and Week 1 through 48 ]
    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).

  6. Kaplan-Meier (K-M) Estimates of Duration of RBC Transfusion Independence of 8 Weeks or More in Participants Who Responded During Week 1 Through Week 24 [ Time Frame: Transfusion status was assessed from every 3 weeks until 16 weeks after the last dose of study drug or at end of treatment, whichever occurred later; median duration of treatment was 50.9 weeks for luspatercept as of the data cut-off date of 01 July 2019. ]
    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 from unstratified K-M method.

  7. Kaplan-Meier Estimates of Duration of RBC Transfusion Independence of 8 Weeks or More in Participants Who Responded During Week 1 Through Week 48 [ Time Frame: Transfusion status was assessed from every 3 weeks until 16 weeks after the last dose of study drug or at end of treatment, whichever occurred later; median duration of treatment was 50.9 weeks for luspatercept as of the data cut-off date of 01 July 2019. ]
    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 is from un-stratified Kaplan-Meier Method

  8. 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 [ Time Frame: Baseline and at Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, extension treatment phase cycle (EC) D1 EC3 D1, EC5 D1, EC7 D1, and end of treatment (EoT) ]
    The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. 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 and a positive change from Baseline score indicates better functioning.

  9. Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score [ Time Frame: Baseline and at Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, extension treatment phase cycle (EC) D1 EC3 D1, EC5 D1, EC7 D1, and end of treatment (EoT) ]
    The EORTC questionnaire was a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Physical Functioning was scored between 0 and 100, with a high score indicating better physcial functioning. Negative change from baseline values indicate deterioration in physical functioning and positive values indicate improvement.

  10. Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score [ Time Frame: Baseline and at Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, extension treatment phase cycle (EC) D1 EC3 D1, EC5 D1, EC7 D1, and end of treatment (EoT) ]
    The EORTC questionnaire was a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Emotional Functioning was scored between 0 and 100, with a high score indicating better emotional functioning. Negative change from baseline values indicate deterioration in emotional functioning and positive values indicate improvement.

  11. Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Score [ Time Frame: Baseline and at Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, extension treatment phase cycle (EC) D1 EC3 D1, EC5 D1, EC7 D1, and end of treatment (EoT) ]
    The EORTC questionnaire was a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 fatigue scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).

  12. Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Score [ Time Frame: Baseline and at Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, extension treatment phase cycle (EC) D1 EC3 D1, EC5 D1, EC7 D1, and end of treatment (EoT) ]
    The EORTC questionnaire was a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from baseline values indicate reduction in dyspnea (i.e. improvement in symptom) and positive values indicate increases in dyspnea (i.e. worsening of symptom).

  13. Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period During the Treatment Period [ Time Frame: Week 1 through Week 24 and Week 1 Through Week 48 ]
    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.

  14. Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period During the Treatment Period [ Time Frame: Week 1 through Week 24 and Week 1 Through Week 48 ]

    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%

  15. Change From Baseline in Mean Serum Ferritin [ Time Frame: Baseline and Weeks 9 to 24 and Weeks 33 to 48 ]
    Mean change from baseline in mean serum ferritin averaged over 9 weeks to 24 weeks and weeks 33 to 48. The mean serum ferritin decrease was the change calculated as the difference of postbaseline mean serum ferritin and baseline mean serum ferritin.

  16. Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT) [ Time Frame: Baseline and Weeks 9 to 24 and Weeks 33 to 48 ]
    Mean change from baseline in mean daily dose of ICT averaged over 9 weeks to 24 weeks and weeks 33 to 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.

  17. Time to Red Blood Cell Transfusion Independence of 8 Weeks or More for Responses Achieved During Week 1 Through 24 [ Time Frame: From first dose to Week 24; Week 1 Through 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 the Primary Phase of the Treatment Period (Week 1 through Week 24 and Week 1 through Week 48).

  18. Time to Red Blood Cell Transfusion Independence of 8 Weeks or More for Responses Achieved During Week 1 Through 48 [ Time Frame: From first dose to 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 from the first dose if IP to Week 48).

  19. Percentage of Participants Who Progressed to Acute Myelogenous Leukemia (AML) [ Time Frame: From Day 1 of study drug up to the data cut off date of 01 July 2019; maximum follow-up time was 26.2 months in the luspatercept arm and 21.8 months in the placebo arm. ]
    For all participants who received at least one dose of study drug, continuous monitoring for progression to AML occurred up until the date of the date cut off date of 01 July 2019.

  20. Kaplan-Meier Estimate for Time to Acute Myelogenous Leukemia Progression [ Time Frame: From Day 1 of study drug up to the data cut off date of 01 July 2019; maximum follow-up time was 26.3 months in the luspatercept arm and 26.1 months in the placebo arm. ]
    Time to AML progression was defined as the time between randomization date and 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.

  21. Kaplan Meier Estimate for Overall Survival [ Time Frame: From Day 1 of study drug up to the data cut off date of 01 July 2019; median follow up time was 26.3 months for luspatercept and 26.1 months for placebo ]
    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.

  22. Number of Participants With Treatment Emergent Adverse Events (TEAE) [ Time Frame: From date of first dose of study drug up to 42 days after the last dose as of the data cut off date of 01 July 2019; maximum duration of treatment in the luspatercept arm was 172 weeks and 103 weeks in the placebo arm ]

    Treatment-emergent adverse events were defined as AEs and included AEs that started on or after the day of the first dose and on or before 42 days after the last dose of IP. A serious adverse event (SAE) is any:

    • Death;
    • Life-threatening event;
    • Any inpatient hospitalization or prolongation of existing hospitalization;
    • Persistent or significant disability or incapacity;
    • Congenital anomaly or birth defect;
    • Any other important medical event

    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.


  23. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F) [ 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. ]
    Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ).

  24. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F) [ 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. ]
    Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ.

  25. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2) [ 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. ]
    Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz.

  26. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax) [ 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. ]
    Tmax was defined as the observed time to maximum plasma concentration of luspatercept.

  27. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax) [ 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. ]
    Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time.

  28. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at 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. ]
    Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state.

  29. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss) [ 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. ]
    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.

  30. Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA) [ Time Frame: From the pre-dose date of first dose of study drug up to the data cut off date of 08 May 2018; maximum duration of exposure to treatment was 114 weeks. ]
    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."



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02631070


Locations
Show Show 74 study locations
Sponsors and Collaborators
Celgene
Acceleron Pharma, Inc.
Investigators
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Study Director: Rodrigo Ito, MD Celgene
  Study Documents (Full-Text)

Documents provided by Celgene:
Study Protocol  [PDF] May 9, 2017
Statistical Analysis Plan  [PDF] May 31, 2018

Publications of Results:
Other Publications:
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02631070    
Other Study ID Numbers: ACE-536-MDS-001
2015-003454-41 ( EudraCT Number )
First Posted: December 15, 2015    Key Record Dates
Results First Posted: May 22, 2020
Last Update Posted: May 22, 2020
Last Verified: May 2020
Keywords provided by Celgene:
MEDALIST
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
MDS
IPSS-R very low/IPSS-R low/IPSS-R intermediate
Additional relevant MeSH terms:
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Preleukemia
Anemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms