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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Celgene Corporation Identifier:
First received: November 27, 2012
Last updated: December 22, 2015
Last verified: December 2015
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 Intervention Phase
Myelodysplastic Syndromes (MDS)
Chronic Myelomonocytic Leukemia (CMML)
Low to Intermediate-1 MDS
Drug: Sotatercept
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Erythroid Hematological Improvement (HI-E) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Adverse Event [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events

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

  • Duration to Erythroid Hematological Improvement (HI-E) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    The length of time between first and last assessment of HI-E

  • Time to progression to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Time from baseline until progression to AML

  • Time to progression to events of higher risk MDS [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Time from baseline until progression to events of higher risk MDS

  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Number of participants who survive without progressing.

  • Overall survival (OS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Number of participants who survive

  • Pharmacokinetics-Cmax [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    Maximum observed concentration in serum

  • Pharmacokinetics-Tmax [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    Time to maximum observed concentration serum

  • Pharmacokinetics- AUC [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve

Enrollment: 74
Study Start Date: November 2012
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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

Detailed Description:
Following enrollment of the initial 3 arms; additional cohorts of 20 patients for intermediate cohorts (not to exceed 2.0 mg/kg) may be added at the time of dose escalation up to 1.0 mg/kg and up to 2.0 mg/kg (eg, 0.75 mg/kg or 1.5 mg/kg respectively) based on assessment by the Steering Committee of available safety and efficacy data when at least six subjects have at least three cycles of treatment in the current dose level.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 defined as requiring transfusion of ≥ 2 units of red blood cells (RBCs) within 84 days of enrollment for hemoglobulin (Hgb) ≤ 9.0 g/dL

No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or erythropoetin (EPO) > 500 mU/ml

No response or loss of response to no greater than 2 prior lines of treatment for myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML) not including ESAs or lines discontinued due to intolerance.

Eastern Cooperative Group (ECOG) score ≤ 2.

Adequate renal function reflected by creatinine < 1.5 X Upper Limit of the Normal (ULN) and creatinine clearance of 50 ml/min according to Cockcroft-Gault formula

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 Normal (ULN)

Free of metastatic malignancy (other than myelodysplastic syndromes (MDS)) for ≥ 2 years

Exclusion Criteria:

Patients with MDS with chromosome 5q deletion without documented treatment failure to lenalidomide (ie, loss of response or no response after 4 months of treatment, intolerable to treatment, or having other cytopenia precluding use of treatment).

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

Subjects requiring ongoing anticoagulant therapy during course of study. Aspirin is allowed.

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 myelodysplastic syndromes (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

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01736683

United States, Colorado
Rocky Mountain Cancer Center-Midtown
Denver, Colorado, United States, 80218
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana-Farber / Harvard Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Monter Cancer Center, North Shore LIJ Health Systems
Lake Success, New York, United States, 11042
Columbia University Medical Center/New York-Presbyterian Hospital
New York, New York, United States, 10032
United States, Ohio
The Cleveland Clinic Foundation Hematology and Medical Oncology / Rm 35
Cleveland, Ohio, United States, 44195
United States, Tennessee
Sarah Cannon Research Inst
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology Round Rock Cancer Center - Round Rock
Round Rock, Texas, United States, 78681
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Texas Oncology, P.A. - Tyler
Tyler, Texas, United States, 75702
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Yakima Valley Memorial Hospital/ North Star Lodge
Yakima, Washington, United States, 98902
Centre Hospitalier Universitaire d'Avicennes
Bobigny Cedex, France, 93009
Institute Paoli-Calmettes Service Haematology
Bp 156,, France, 13273
CHRU de Lille -Hôpital Claude Huriez Service des Maladies du Sang
Lille, France, 59037
CHRU Nantes
Nantes, France, 44093
Hôpital CochinHématologie
Paris Cedex 14, France, 75679
Centre Henri Becquerel
Rouen, France, 79038
CHU Purpan
Toulouse, France, 31059
Sponsors and Collaborators
Celgene Corporation
Study Director: Abderrahmane Laadem Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation Identifier: NCT01736683     History of Changes
Other Study ID Numbers: ACE-011-MDS-001 
Study First Received: November 27, 2012
Last Updated: December 22, 2015
Health Authority: United States: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Celgene Corporation:
intermediate-1 risk myelodysplastic syndromes
low risk myelodysplastic syndromes (MDS)
phase 2
Non-proliferative chronic myelomonocytic leukemia (CMML)

Additional relevant MeSH terms:
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions processed this record on February 07, 2016