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

This study has been terminated.
(The study was stopped after the interim analysis based on lack of sufficient efficacy. There were no safety concerns.)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01513317
First received: October 21, 2011
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Siltuximab
Drug: Placebo
Drug: Best supportive care (BSC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Proportion of patients achieving a reduction in red blood cell transfusions [ Time Frame: 8 weeks before the unblinding compared with RBC transfusions in the 8 weeks before the date the informed consent form was signed ] [ Designated as safety issue: No ]
    Reduction in red blood cell transfusions is defined by >=50% relative decrease and a >=2 unit absolute decrease in red blood cell transfusions.


Secondary Outcome Measures:
  • Change in hemoglobin [ Time Frame: Baseline to Week 13 ] [ Designated as safety issue: No ]
  • Change in percentage of bone marrow blasts [ Time Frame: Baseline to Week 13 ] [ Designated as safety issue: No ]
  • Anemia symptom improvement [ Time Frame: Baseline to Week 13 ] [ Designated as safety issue: No ]
    The improvement is measured by the Non-Chemotherapy Anemia Symptom Scale (NCA-SS) and Functional Assessment of Cancer Therapy-Anemia (FACT-An). The (NCA-SS) is an 11-point rating scale ranging from 0 (not at all) to 10 (worst imaginable). This instrument is developed for use in non-chemotherapy-related anemia subjects. The FACT-An is used to assess functional status and symptoms of MDS.

  • Number of RBC units transfused [ Time Frame: 8 weeks before the unblinding ] [ Designated as safety issue: No ]
  • Proportion of subjects who do not require RBC transfusions [ Time Frame: 8 weeks before the unblinding ] [ Designated as safety issue: No ]

Enrollment: 76
Study Start Date: November 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Siltuximab + Best supportive care (BSC)
Group A: siltuximab (15 mg/kg) administered as a 1-hour infusion every 4 weeks + 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 + BSC
Group B: placebo administered as a 1-hour infusion every 4 weeks + BSC
Drug: Placebo
Administered as a 1-hour intravenous infusion every 4 weeks
Drug: Best supportive care (BSC)
Best supportive care according to local standards and guidelines

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01513317

Locations
United States, Florida
Tampa, Florida, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, New York
New York, New York, United States
United States, North Carolina
Winston-Salem, North Carolina, United States
United States, Texas
Houston, Texas, United States
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
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01513317     History of Changes
Other Study ID Numbers: CR100752, CNTO328MDS2001, 2011-000261-12
Study First Received: October 21, 2011
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration
Spain: Comite Etico de Investigacion Clinica
Spain: Spanish Agency of Medicines

Keywords provided by Janssen Research & Development, LLC:
Myelodysplastic Syndrome
MDS
Blood and lymphatic diseases
Siltuximab
Anemic

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014