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Trial record 1 of 1 for:    NCT02631070
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A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MEDALIST)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02631070
First Posted: December 15, 2015
Last Update Posted: October 2, 2017
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.
Collaborator:
Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Celgene
  Purpose

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 subjects with anemia due to IPSS-R very low, low, or intermediate MDS with ring sideroblasts who require RBC transfusions.


Condition Intervention Phase
Myelodysplastic Syndromes Drug: Luspatercept Other: Placebo Phase 3

Study Type: Interventional
Study Design: 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.

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks [ Time Frame: Week 1 through week 24 ]
    Proportion of subjects who are red blood cell (RBC) transfusion free over any consecutive 56-day period within week 1 through week 24


Secondary Outcome Measures:
  • Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 weeks [ Time Frame: Up to approximately 48 weeks ]
    Proportion of subjects who are Red blood cell (RBC) transfusion free over any consecutive 84-day period within week 1 through 24 and week 1 through 48

  • Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks [ Time Frame: Up to approximately 48 weeks ]
    Proportion of subjects who are Red blood cell (RBC) transfusion free over any consecutive 56-day period within week 1 through week 48

  • Reduction in red blood cell (RBC) units transfused over 16 weeks [ Time Frame: Up to approximately 48 weeks ]
    Mean change in total Red blood cell (RBC) units transfused over a fixed 16-week period within week 8 trough 24 and week 32 through 48

  • Proportion of subjects achieving Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG) over any consecutive 56 days [ Time Frame: Up to approximately 48 weeks ]
    Proportion of subjects achieving modified Hematological improvement-erythroid (HI-E) over any consecutive 56-day period during the treatment period

  • Mean hemoglobin increase ≥ 1.0 g/dL [ Time Frame: Up to approximately 48 weeks ]
    Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.0 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions

  • Duration of Red Blood Cell Transfusion Independence (RBC-TI) [ Time Frame: Up to approximately 3.5 years ]
    Maximum duration of red blood cell (RBC) transfusion independence for subjects who achieve RBC TI ≥ 8 weeks

  • Change in EORTC QLQ-C30 score [ Time Frame: Up to approximately 3.5 years ]
    Change in EORTC QLQ-C30 scores per scheduled visits

  • Hematologic improvement - neutrophils (HI-N) per International Working Group (IWG) [ Time Frame: Up to approximately 48 weeks ]
    Proportion of subjects achieving HI-N over any consecutive 56-day period

  • Mean decrease in serum ferritin [ Time Frame: Up to approximately 48 weeks ]
    Change in serum ferritin over scheduled assessments

  • Mean decrease in iron chelation therapy (ICT) use [ Time Frame: Up to approximately 48 weeks ]
    The change in daily dose for each subject is calculated as the difference of post-baseline mean daily dose and baseline mean daily dose. Analysis of covariance (ANCOVA) will be used to compare the treatment difference between groups, with the stratification factors and baseline ICT value as covariates.

  • Time to red blood cell transfusion independence (RBC-TI) [ Time Frame: Up to approximately 48 weeks ]
    Time between randomization and the date onset of TI is first observed (ie, Day 1 of 56 days without any RBC transfusions).

  • Number of subjects progressing to acute myeloid leukemia (AML) [ Time Frame: Up to approximately 3 years ]
    Assessments/measurements that were collected in different units of measure will be aggregated and presented by standard units for the study.

  • Time to progression to acute myeloid leukemia (AML) [ Time Frame: Up to approximately 3 years ]
    Is defined as the time between randomization and first diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.

  • Overall survival (OS) [ Time Frame: Up to approximately 3.5 years ]
    Overall survival is defined as the time from date of randomization to death due to any cause

  • Adverse Events (AEs) [ Time Frame: Up to approximately 3.5 years ]
    Type, frequency, severity of AEs and relationship of AEs to luspatercept/placebo

  • Frequency of anti-drug antibodies (ADA) [ Time Frame: Up to approximately 3.5 years ]
    Will be collected for assessment of anti-drug antibodies (ADA) against luspatercept in serum in all subjects

  • Pharmacokinetics - AUC [ Time Frame: Up to approximately 1 year ]
    Area under the plasma concentration-time curve

  • Pharmacokinetics ‐ Cmax [ Time Frame: Up to approximately 1 year ]
    Maximum observed concentration in plasma


Enrollment: 229
Actual Study Start Date: February 9, 2016
Estimated Study Completion Date: June 25, 2019
Estimated Primary Completion Date: June 25, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.

  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 ESA treatment, defined as:

    • Refractory to prior Erythropoiesis- stimulating agents(ESA) 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 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 a bone marrow aspirate stain for iron, calculated transferrin saturation (iron/total iron binding capacity) ≤ 20%, or serum ferritin ≤ 15 μg/L 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

  Contacts and Locations
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


  Show 74 Study Locations
Sponsors and Collaborators
Celgene
Acceleron Pharma, Inc.
Investigators
Study Director: Abderrahmane Laadem, MD Celgene
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02631070     History of Changes
Other Study ID Numbers: ACE-536-MDS-001
First Submitted: November 10, 2015
First Posted: December 15, 2015
Last Update Posted: October 2, 2017
Last Verified: September 2017

Keywords provided by Celgene:
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

Additional relevant MeSH terms:
Syndrome
Anemia
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms