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 currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01736683
First received: November 27, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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
Anemia
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
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).

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


Estimated Enrollment: 100
Study Start Date: November 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sotatercept 1.0 mg/kg Drug: Sotatercept
Sotatercept 1.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: (ActRIIA-IgG1Fc)
Experimental: Sotatercept 2.0 mg/kg Drug: Sotatercept
Sotatercept 2.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: (ActRIIA-IgG1Fc)
Experimental: Sotatercept 0.5 mg/kg Drug: Sotatercept
Sotatercept 0.5 mg/kig subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
Other Name: (ActRIIA-IgG1Fc)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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:

  • 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 ClinicalTrials.gov identifier: NCT01736683

Contacts
Contact: Christopher Powell 908-673-2259 cpowell@celgene.com

Locations
United States, Colorado
Rocky Mountain Cancer Centers Recruiting
Denver, Colorado, United States, 80218
United States, Florida
H. Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33602
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana-Farber Cancer Institute/Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
North Shore-LIJ Health System Monter Cancer Center Recruiting
Lake Success, New York, United States, 11020
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Texas Oncology Completed
Round Rock, Texas, United States, 78681
Texas Oncology Recruiting
Tyler, Texas, United States, 75702
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
United States, Washington
Yakima Valley Memorial Hospital/North Star Lodge Recruiting
Yakima, Washington, United States, 98902
France
Centre Hospitalier Universitaire Hôpital Avicenne Recruiting
Bobigny, France, 93009
CHRU de Lille -Hôpital Claude Huriez Service des Maladies du Sang Recruiting
Lille, France, 59037
CHU De Nantes Recruiting
Nanes, France, 44000
Hôpital Cochin Completed
Paris Cedex, France, 75001
Centre de Recherche en Cancerologie de Marseille- Institute Paoli Calmettes Recruiting
Rouen, France, 13273
Centre Henri Becquerel Recruiting
Rouen Cedex 1, France, 76038
CHU Purpan Recruiting
Toulouse, France, 31059
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Abderrahmane Laadem Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01736683     History of Changes
Other Study ID Numbers: ACE-011-MDS-001
Study First Received: November 27, 2012
Last Updated: August 4, 2014
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:
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:
Anemia
Leukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on August 19, 2014