Clinical trial NCT01736683: Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-11-29
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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 /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

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

Primary outcomes:
measure: Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
timeFrame: Day 2 to Day 142
Secondary outcomes:
measure: Time to Erythroid Hematological Improvement (HI-E) Response
timeFrame: Day 1 to Day 87
measure: Duration of Erythroid Hematological Improvement (HI-E)
timeFrame: Day 1 to 183.7 weeks
measure: Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression
timeFrame: Day 1 to 183.7 weeks
measure: Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression
timeFrame: Day 1 to 257.3 weeks
measure: Kaplan-Meier Estimates for Progression-free Survival
timeFrame: Day 1 to 257.3 weeks
measure: Kaplan-Meier Estimates for Overall Survival (OS)
timeFrame: Day 1 to 257.3 weeks
measure: Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints
timeFrame: Cycle 1 Day 8 and !5 up to Cycle 2 Day 1
measure: Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Day 1 up to 59.2 months
measure: Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to 59.2 months
measure: Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval
timeFrame: Day 2 to Day 142
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Midtown
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana-Farber / Harvard Cancer Institute
state: Massachusetts
city: Lake Success
country: United States
facility: Monter Cancer Center, North Shore LIJ Health Systems
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/New York-Presbyterian Hospital
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation Hematology and Medical Oncology Rm 35
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Inst
state: Tennessee
city: Round Rock
country: United States
facility: Texas Oncology Round Rock Cancer Center - Round Rock
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/ North Star Lodge
state: Washington
city: Bobigny Cedex
country: France
facility: Centre Hospitalier Universitaire d'Avicennes
city: Bp 156,
country: France
facility: Institute Paoli-Calmettes Service Haematology
city: Lille
country: France
facility: CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang
city: Nantes
country: France
facility: CHRU Nantes
city: Paris Cedex 14
country: France
facility: Hopital Cochin Hematologie
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: CHU Purpan
Study officials:
affiliation: Celgene Corporation
name: Rodrigo Ito, MD
role: STUDY_DIRECTOR
References:
citation: 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.