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

Myelodysplastic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01513317
• Other study ID #: CR100752
• Secondary ID: CNTO328MDS200120
• Status: Terminated
• Phase: Phase 2
• First received: October 21, 2011
• Last updated: September 24, 2014
• Start date: November 2011
• Est. completion date: September 2012

Study information

• Verified date: September 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Comite Etico de Investigacion ClinicaSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 76
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Siltuximab
15 mg/kg administered as a 1-hour intravenous infusion every 4 weeks
• Placebo
Administered as a 1-hour intravenous infusion every 4 weeks
• Best supportive care (BSC)
Best supportive care according to local standards and guidelines

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Netherlands,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change From Baseline in the Mean Hemoglobin Concentrations at Week 13		Baseline and Week 13	No
Secondary	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	No
Secondary	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	No
Secondary	Mean Changes From Baseline in Percentages of Bone Marrow Blast Cells at Week 13		Baseline and Week 13	No
Secondary	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	No