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

November 27, 2012
August 4, 2014
November 2012
June 2015   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01736683 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
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).

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Anemia
  • Myelodysplastic Syndromes (MDS)
  • Chronic Myelomonocytic Leukemia (CMML)
  • Low to Intermediate-1 MDS
  • Drug: Sotatercept
    Sotatercept 1.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
    Other Name: (ActRIIA-IgG1Fc)
  • Drug: Sotatercept
    Sotatercept 2.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
    Other Name: (ActRIIA-IgG1Fc)
  • Drug: Sotatercept
    Sotatercept 0.5 mg/kig subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
    Other Name: (ActRIIA-IgG1Fc)
  • Experimental: Sotatercept 1.0 mg/kg
    Intervention: Drug: Sotatercept
  • Experimental: Sotatercept 2.0 mg/kg
    Intervention: Drug: Sotatercept
  • Experimental: Sotatercept 0.5 mg/kg
    Intervention: Drug: Sotatercept
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
May 2017
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Christopher Powell 908-673-2259 cpowell@celgene.com
United States,   France
 
NCT01736683
ACE-011-MDS-001
No
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Abderrahmane Laadem Celgene Corporation
Celgene Corporation
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP