A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Patients With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome

Phase 2

Terminated

• Conditions: Myelodysplastic Syndrome
• Interventions: Drug: Placebo; Drug: Siltuximab; Drug: Best supportive care (BSC)

• Registration Number: NCT01513317
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to evaluate the efficacy of siltuximab, demonstrated by a reduction in red blood cell (RBC), transfusions to treat the anemia of Myelodysplastic Syndrome (MDS).

Detailed Description

The study treatments will be administered double-blind for 12 weeks, meaning that the patient and study personnel will not know the identity of the treatment. Approximately 75 patients will be randomized (patients are assigned to a treatment by a chance) in a 2:1 ratio to receive siltuximab plus best supportive care (BSC) (Group A) or placebo plus BSC (Group B). BSC includes RBC transfusion, antimicrobials, white blood cell (WBC) growth factors, and platelet transfusions. Patients who complete 12 weeks of treatment may qualify to receive siltuximab as open-label (identity of treatment will be known) treatment. Treatment may continue until death, unacceptable toxicity, withdrawal of consent, or the clinical cutoff (defined as 24 weeks after the last patient is randomized), whichever occurs first. The study will end approximately 36 weeks after the last patient is randomized. Patient safety will be monitored. Siltuximab and matching placebo will be supplied as a sterile, lyophilized formulation for reconstitution and intravenous (IV) infusion. Group A: siltuximab (15 mg/kg) administered as a 1-hour infusion every 4 weeks + BSC, or Group B: placebo administered as a 1-hour infusion every 4 weeks + BSC.

Study Timeline

• Study First Submitted: 2011-10-21
• Study Start: 2011-11
• Study First Submitted QC: 2012-01-16
• Study First Posted: 2012-01-20
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Disposition First Submitted: 2013-10-04
• Disposition First Submitted QC: 2013-10-04
• Disposition First Posted: 2013-10-28
• Status Verified: 2014-09
• Results First Submitted: 2014-09-24
• Results First Submitted QC: 2014-09-24
• Last Update Submitted: 2014-09-24
• Results First Posted: 2014-09-29
• Last Update Posted: 2014-09-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

• Confirmed diagnosis of myelodysplastic syndrome (MDS), according to World Heath Organization or the French-American-British Cooperative Group pathologic classification, with an International Prognostic Scoring System score 0, 0.5, or 1.0, indicating Low- or INT-1-risk disease.
• Documented RBC transfusion of at least 2 units of RBC for the treatment of the anemia of MDS in the 8 weeks preceding the start of the Screening Period.
• Adequate iron stores, demonstrated by either the presence of stainable iron in the bone marrow or a serum ferritin of > 100 ng/mL.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
• Symptomatic anemia (defined by a score > 0 on the Non-Chemotherapy Anemia Symptom Scale [NCA-SS]).

Exclusion Criteria

• Had treatment with drugs or other agents targeting IL-6 or its receptor within 4 weeks of randomization.
• Any condition that, in the opinion of the investigator, would make participation not in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments.
• Patients with Chronic Myelomonocytic Leukemia (CMML).
• Causes other than MDS contributing to anemia, such as Vitamin B12 or folate deficiency, bleeding, hemolysis, hemoglobinopathy, or chronic renal failure.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Siltuximab	Best supportive care (BSC)	15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo	Placebo	Placebo administered as a 1-hour infusion every 4 weeks + BSC
Placebo	Best supportive care (BSC)	Placebo administered as a 1-hour infusion every 4 weeks + BSC
Siltuximab	Siltuximab	15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Reduction in Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS)	Up to Week 13	Reduction in RBC transfusions to treat the anemia of MDS is defined as a ≥50 percentage relative decrease and a ≥2 unit absolute decrease in RBC transfusions in the 8 weeks before the unblinding (scheduled to occur after 12 weeks of treatment) compared with RBC transfusions in the 8 weeks before the date the informed consent form was signed.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Hemoglobin Improvement (≥1.5 g/dL Increase From Baseline) Unrelated to Red Blood Cell (RBC) Transfusion at Week 13	Week 13
Percentage of Participants Who Did Not Require a Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) in the 8 Weeks of Treatment Before Unblinding at Week 13	8 weeks
Mean Changes From Baseline in Percentages of Bone Marrow Blast Cells at Week 13	Baseline and Week 13
Median Number of Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) During the 8 Weeks of Treatment Before Unblinding at Week 13	8 weeks
Change From Baseline in the Mean Hemoglobin Concentrations at Week 13	Baseline and Week 13