Clinical trial NCT01513317: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Keywords: Myelodysplastic Syndrome
MDS
Blood and lymphatic diseases
Siltuximab
Anemic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-01-20
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Reduction in Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS)
timeFrame: Up to Week 13
Secondary outcomes:
measure: Change From Baseline in the Mean Hemoglobin Concentrations at Week 13
timeFrame: Baseline and Week 13
measure: Percentage of Participants Achieving Hemoglobin Improvement (≥1.5 g/dL Increase From Baseline) Unrelated to Red Blood Cell (RBC) Transfusion at Week 13
timeFrame: Week 13
measure: 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
timeFrame: 8 weeks
measure: Mean Changes From Baseline in Percentages of Bone Marrow Blast Cells at Week 13
timeFrame: Baseline and Week 13
measure: 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
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Houston
country: United States
state: Texas
city: Box Hill
country: Australia
city: Camperdown
country: Australia
city: St Leonards
country: Australia
city: Antwerpen
country: Belgium
city: Brugge
country: Belgium
city: Gent
country: Belgium
city: Yvoir
country: Belgium
city: Den Haag
country: Netherlands
city: Dordrecht
country: Netherlands
city: Krasnodar
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Oviedo (Asturias)
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Stockholm
country: Sweden
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: