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

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Subjects With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome

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).

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Siltuximab; Drug: Best supportive care (BSC); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia
  • Camperdown, Australia
  • St Leonards, Australia
• Belgium
  • Antwerpen, Belgium
  • Brugge, Belgium
  • Gent, Belgium
  • Yvoir, Belgium
• Netherlands
  • Den Haag, Netherlands
  • Dordrecht, Netherlands
• Russian Federation
  • Krasnodar, Russian Federation
  • Moscow N/A, Russian Federation
  • Nizhny Novgorod, Russian Federation
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Oviedo (Asturias), Spain
  • Salamanca, Spain
  • Valencia, Spain
• Sweden
  • Stockholm, Sweden
• United States
  • Florida
    • Tampa, Florida, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Winston-Salem, North Carolina, United States
  • Texas
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Siltuximab; 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Drug: Siltuximab; 15 mg/kg administered as a 1-hour intravenous infusion every 4 weeks; Drug: Best supportive care (BSC); Best supportive care according to local standards and guidelines
Experimental: Placebo; Placebo administered as a 1-hour infusion every 4 weeks + BSC	Drug: Best supportive care (BSC); Best supportive care according to local standards and guidelines; Drug: Placebo; Administered as a 1-hour intravenous infusion every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Reduction in Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS)	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.	Up to Week 13

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in the Mean Hemoglobin Concentrations at Week 13	Baseline and Week 13
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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: October 21, 2011
• First Submitted That Met QC Criteria: January 16, 2012
• First Posted (Estimate): January 20, 2012

Study Record Updates

• Last Update Posted (Estimate): September 29, 2014
• Last Update Submitted That Met QC Criteria: September 24, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: MDS; Myelodysplastic Syndrome; Blood and lymphatic diseases; Siltuximab; Anemic
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Antineoplastic Agents; Siltuximab
• Other Study ID Numbers: CR100752; CNTO328MDS2001 (Other Identifier: Janssen Research & Development, LLC); 2011-000261-12 (EudraCT Number)