Overview

This trial is active, not recruiting.

Conditions anemia, myelodysplastic syndromes (mds), chronic myelomonocytic leukemia (cmml), low to intermediate-1 mds
Treatments sotatercept
Phase phase 2
Sponsor Celgene Corporation
Start date November 2012
End date August 2015
Trial size 74 participants
Trial identifier NCT01736683, ACE-011-MDS-001

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Sotatercept 0.1 mg/kg
sotatercept
Sotatercept 0.1 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
(Experimental)
Sotatercept 0.3 mg/kg
sotatercept ActRIIA-IgG1Fc
Sotatercept 0.3 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
(Experimental)
Sotatercept 0.5 mg/kg
sotatercept
Sotatercept 0.5 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
(Experimental)
Sotatercept 1.0 mg/kg
sotatercept
Sotatercept 1.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
(Experimental)
Sotatercept 1.5 mg/kg
sotatercept ActRIIA-IgG1Fc
Sotatercept 1.5 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles
(Experimental)
Sotatercept 2.0 mg/kg
sotatercept
Sotatercept 2.0 mg/kg subcutaneous (SC) once every 3 weeks (q3W) for 5 cycles

Primary Outcomes

Measure
Erythroid Hematological Improvement (HI-E)
time frame: Up to 24 weeks

Secondary Outcomes

Measure
Adverse Event
time frame: Up to 3 years
Red Blood Cell (RBC) Transfusion Independence
time frame: Up to 24 weeks
Duration to Erythroid Hematological Improvement (HI-E)
time frame: Up to 24 weeks
Time to progression to Acute Myeloid Leukemia (AML)
time frame: Up to 2 years
Time to progression to events of higher risk MDS
time frame: Up to 2 years
Progression-free survival (PFS)
time frame: Up to 2 years
Overall survival (OS)
time frame: Up to 2 years
Pharmacokinetics-Cmax
time frame: Up to 24 weeks
Pharmacokinetics-Tmax
time frame: Up to 24 weeks
Pharmacokinetics- AUC
time frame: Up to 24 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Celgene Corporation.