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Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)

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ClinicalTrials.gov Identifier: NCT01736683
Recruitment Status : Active, not recruiting
First Posted : November 29, 2012
Last Update Posted : March 6, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
The primary objective of this study is to determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of improvement of anemia in patients diagnosed with low- or intermediate-1 risk MDS or non-proliferative chronic myelomonocytic leukemia (CMML).

Condition or disease Intervention/treatment Phase
Anemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Low to Intermediate-1 MDS Myelodysplastic Syndromes (MDS) Chronic Myelomonocytic Leukemia (CMML) Drug: Sotatercept Drug: Sotatercept 0.1 mg/kg Drug: Sotatercept 0.3 mg/kg Drug: Sotatercept 0.5 mg/kg Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Phase 2, Parallel, Dose-ranging, Multicenter Study of Sotatercept for the Treatment of Patients With Anemia and Low- or Intermediate-1 Risk Myelodysplastic Syndromes or Non-proliferative Chronic Myelomonocytic Leukemia (CMML).
Actual Study Start Date : November 28, 2012
Estimated Primary Completion Date : April 20, 2018
Estimated Study Completion Date : April 20, 2018


Arm Intervention/treatment
Experimental: Sotatercept 0.1 mg/kg
Sotatercept 0.1 mg/kg
Drug: Sotatercept
Sotatercept 0.1 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Drug: Sotatercept 0.1 mg/kg
Sotatercept 0.1 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: ActRIIA-IgG1Fc
Experimental: Sotatercept 0.3 mg/kg
Sotatercept 0.3 mg/kg
Drug: Sotatercept
Sotatercept 0.3 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: ActRIIA-IgG1Fc
Drug: Sotatercept 0.3 mg/kg
Sotatercept 0.3 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: ActRIIA-IgG1Fc
Experimental: Sotatercept 0.5 mg/kg
Sotatercept 0.5 mg/kg
Drug: Sotatercept
Sotatercept 0.5 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Drug: Sotatercept 0.5 mg/kg
Sotatercept 0.5 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: ActRIIA-IgG1c
Experimental: Sotatercept 1.0 mg/kg
Sotatercept 1.0 mg/kg
Drug: Sotatercept
Sotatercept 1.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Experimental: Sotatercept 1.5 mg/kg
Sotatercept 1.5 mg/kg
Drug: Sotatercept
Sotatercept 1.5 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: ActRIIA-IgG1Fc
Experimental: Sotatercept 2.0 mg/kg
Sotatercept 2.0 mg/kg
Drug: Sotatercept
Sotatercept 2.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles



Primary Outcome Measures :
  1. Erythroid Hematological Improvement (HI-E) [ Time Frame: Up to 24 weeks ]
    HI-E (for subjects that require a transfusion of <4 units of RBCs) is an increase ≥1.5 g/dL Hgb sustained over a period ≥8 weeks in the absence of RBC transfusion; or HI-E (for subjects that require a transfusion of ≥4 units of RBCs) is a decrease ≥4 units of RBCs transfused over a period of 8 weeks


Secondary Outcome Measures :
  1. Adverse Event [ Time Frame: Up to 3 years ]
    Number of participants with adverse events

  2. Red Blood Cell (RBC) Transfusion Independence [ Time Frame: Up to 24 weeks ]
    The time between randomization (for Part 1)/start of therapy (for Part 2) and the date the start of HI-E

  3. Duration to Erythroid Hematological Improvement (HI-E) [ Time Frame: Up to 24 weeks ]
    The length of time between first and last assessment of HI-E

  4. Time to progression to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years ]
    Time from baseline until progression to AML

  5. Time to progression to events of higher risk MDS [ Time Frame: Up to 2 years ]
    Time from baseline until progression to events of higher risk MDS

  6. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    Number of participants who survive without progressing.

  7. Overall survival (OS) [ Time Frame: Up to 2 years ]
    Number of participants who survive

  8. Pharmacokinetics-Cmax [ Time Frame: Up to 24 weeks ]
    Maximum observed concentration in serum

  9. Pharmacokinetics-Tmax [ Time Frame: Up to 24 weeks ]
    Time to maximum observed concentration serum

  10. Pharmacokinetics- AUC [ Time Frame: Up to 24 weeks ]
    Area under the plasma concentration-time curve



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women ≥ 18 years of age
  • Documented diagnosis of myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), White blood cells (WBC) ≤ 13,000 /mm3, World Health Organization (WHO)) that meets International Prognostic Scoring System (IPSS) criteria for low or intermediate-1 risk disease
  • Anemia, Hemoglobin (Hgb) ≤ 9.0 g/dL or ≥ 2 units of Red Blood Cells (RBCs) within 84 days
  • No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or erythropoetin (EPO) > 500 mU/ml
  • Eastern Cooperative Group (ECOG) score ≤2.
  • Creatinine < 1.5 X Upper Limit of the Normal (ULN)
  • Total bilirubin ≤3.0 mg/dL
  • Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) & Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic (SGPT) ≤3.0 x Upper Limit of Norma (ULN)
  • Free of metastatic malignancy (other than MDS) for ≥2 years
  • Highly effective methods of birth control for females & males

Exclusion Criteria:

  • Chromosome 5q deletion
  • Pregnant or breast feeding women and males who do not agree to use condom during the sexual contact with females of childbearing potential.
  • Major surgery within 30 days
  • Incomplete recovery or incomplete healing of wounds from previous surgery
  • Heart failure ≥3 (New York Heart Association(NYHA))
  • Thromboembolic or myocardial infarction event within 6 months
  • Concurrent anti-cancer cytotoxic chemotherapy
  • History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant protein
  • Known positive for Human Immunovirus (HIV) or infectious Hepatitis type C or active infectious Hepatitis type B.
  • Clinically significant anemia unrelated to MDS
  • Thrombocytopenia (<30,000/uL)
  • Uncontrolled hypertension
  • Treatment with another investigational drug or device within 28 days prior to Day 1
  • Prior Exposure to Sotatercept (ACE-011)
  • Any serious medical condition, lab abnormality or psychiatric illness

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): NCT01736683


  Show 38 Study Locations
Sponsors and Collaborators
Celgene
Investigators
Study Director: Abderrahmane Laadem Celgene Corporation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01736683     History of Changes
Other Study ID Numbers: ACE-011-MDS-001
First Posted: November 29, 2012    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

Keywords provided by Celgene:
ACE-011
anemia
dose-ranging
intermediate-1 risk myelodysplastic syndromes
low risk myelodysplastic syndromes (MDS)
multicenter
open-label
parallel
phase 2
randomized
Sotatercept
Non-proliferative chronic myelomonocytic leukemia (CMML)
hemoglobin
transfusions

Additional relevant MeSH terms:
Syndrome
Leukemia
Anemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs