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

NCT01736683 | Completed Phase 2 Results DMC

• 3 other identifiers: 7962-017ACE-011-MDS-0012012-002601-22
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 20

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 myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML).

Conditions

Anemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Low to Intermediate-1 MDS; Myelodysplastic Syndromes (MDS); Chronic Myelomonocytic Leukemia (CMML)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)

  The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For transfusion dependence efficacy (TDE) participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.

  Day 2 to Day 142

Secondary Outcomes (10)

• Time to Erythroid Hematological Improvement (HI-E) Response

  Day 1 to Day 87

• Duration of Erythroid Hematological Improvement (HI-E)

  Day 1 to 183.7 weeks

• Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression

  Day 1 to 183.7 weeks

• Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression

  Day 1 to 257.3 weeks

• Kaplan-Meier Estimates for Progression-free Survival

  Day 1 to 257.3 weeks

Study Arms (6)

Sotatercept 0.1 mg/kg

EXPERIMENTAL

Sotatercept 0.1 mg/kg

Drug: Sotatercept

Sotatercept 0.3 mg/kg

EXPERIMENTAL

Sotatercept 0.3 mg/kg

Drug: Sotatercept

Sotatercept 0.5 mg/kg

EXPERIMENTAL

Sotatercept 0.5 mg/kg

Drug: Sotatercept

Sotatercept 1.0 mg/kg

EXPERIMENTAL

Sotatercept 1.0 mg/kg

Drug: Sotatercept

Sotatercept 1.5 mg/kg

EXPERIMENTAL

Sotatercept 1.5 mg/kg

Drug: Sotatercept

Sotatercept 2.0 mg/kg

EXPERIMENTAL

Sotatercept 2.0 mg/kg

Drug: Sotatercept

Interventions

Sotatercept DRUG

Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.

Also known as: ACE-011, ActRIIA-IgG1Fc

Sotatercept 0.1 mg/kg; Sotatercept 0.3 mg/kg; Sotatercept 0.5 mg/kg; Sotatercept 1.0 mg/kg; Sotatercept 1.5 mg/kg; Sotatercept 2.0 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 /mm\^3, 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 \* 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 \* Upper Limit of Norma (ULN)
• Free of metastatic malignancy (other than MDS) for ≥2 years
• Highly effective methods of birth control for females and males

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (20)

Rocky Mountain Cancer Center-Midtown

Denver, Colorado, 80218, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Dana-Farber / Harvard Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Monter Cancer Center, North Shore LIJ Health Systems

Lake Success, New York, 11042, United States

Location

Columbia University Medical Center/New York-Presbyterian Hospital

New York, New York, 10032, United States

Location

The Cleveland Clinic Foundation Hematology and Medical Oncology Rm 35

Cleveland, Ohio, 44195, United States

Location

Sarah Cannon Research Inst

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Round Rock Cancer Center - Round Rock

Round Rock, Texas, 78681, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Yakima Valley Memorial Hospital/ North Star Lodge

Yakima, Washington, 98902, United States

Location

Centre Hospitalier Universitaire d'Avicennes

Bobigny, 93009, France

Location

Institute Paoli-Calmettes Service Haematology

BP 156,, 13273, France

Location

CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang

Lille, 59037, France

Location

CHRU Nantes

Nantes, 44093, France

Location

Hopital Cochin Hematologie

Paris, 75679, France

Location

Centre Henri Becquerel

Rouen, 79038, France

Location

CHU Purpan

Toulouse, 31059, France

Location

Related Publications (1)

• Komrokji R, Garcia-Manero G, Ades L, Prebet T, Steensma DP, Jurcic JG, Sekeres MA, Berdeja J, Savona MR, Beyne-Rauzy O, Stamatoullas A, DeZern AE, Delaunay J, Borthakur G, Rifkin R, Boyd TE, Laadem A, Vo B, Zhang J, Puccio-Pick M, Attie KM, Fenaux P, List AF. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018 Feb;5(2):e63-e72. doi: 10.1016/S2352-3026(18)30002-4. Epub 2018 Jan 10.

  PMID: 29331635 DERIVED

MeSH Terms

Conditions

Anemia; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

800-672-6372

Study Officials

• Rodrigo Ito, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: November 29, 2012
• Study Start: November 28, 2012
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: October 24, 2022
• Results First Posted: June 13, 2019

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

US (13); FR (7)