Primary Objective:The primary objective of this study is to demonstrate that CNTO 328 in combination with BSC is superiorto BSC in terms of objective response (complete response [CR] + partial response [PR]) among subjectswith multicentric Castleman…
ID
Source
Brief title
Condition
- Lymphomas NEC
- Immune disorders NEC
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint will be objective tumor response (CR + PR)
modified to allow assessment of
measurable cutaneous lesions, as measured by Cheson criteria (Cheson et al,
2007; positron-emission
tomography [PET] scan data, if obtained, will not be taken into account).
Other efficacy endpoints include:
• Duration of tumor response (whenever possible, disease progression documented
by the appearance
of new lesions should be confirmed by histologic examination of the new lesions)
• Time to treatment failure
• Change in hemoglobin from baseline to the average of the last 8 weeks of
treatment (through
Week 18)
• Proportion of subjects who are able to discontinue corticosteroids
Patient-reported outcome (PRO) endpoints include:
• Change from baseline in fatigue measured by the Functional Assessment of
Chronic Illness
Therapy-Fatigue (FACIT-F)
• Change from baseline in physical function assessed by the Medical Outcome
Study Short-Form-36
(SF-36) Physical Component Summary (PCS)
• Change from baseline in patient-reported symptom severity measured with the
MCD Symptom
Scale
Secondary outcome
PHARMACOKINETIC EVALUATIONS
Pharmacokinetic endpoints include:
• Cmin
• Cmax
If sufficient data are available, other pharmacokinetic parameters, including
but not limited to t1/2,
AUC(t1-t2), CL, and V may be calculated.
PHARMACODYNAMIC BIOMARKER EVALUATIONS
Assays to be performed include:
• Tissue and blood gene expression profiling
• Immunohistochemistry and serum analysis of proteins relevant to the IL-6
signaling pathway (eg,
hepcidin, CRP)
SAFETY EVALUATIONS
• AEs and AEs >= Grade 3
• SAEs
• Infusion reactions
• Clinically significant abnormal laboratory parameters
• Antibodies to CNTO 328
Background summary
CNTO 328 is a chimeric (murine-human) IgG1* mAb that specifically binds human
IL-6 with high affinity
and prevents its interaction with the IL-6 receptor, glycoprotein (GP) 80
(Seideman and Peritt, 2002). The
chimeric antibody contains the variable region of a murine anti-human IL-6 mAb
and the constant region
from a human immunoglobulin gamma (IgG) 1 molecule. The mechanism of action of
CNTO 328 is
neutralization of IL-6 bioactivity, which can be measured indirectly by
C-reactive protein (CRP)
suppression.
Hypothesis:
The primary hypothesis is that CNTO 328 + BSC will demonstrate a higher overall
response rate than
placebo + BSC, and provide durable clinical benefit with an acceptable
benefit/risk profile.
Study objective
Primary Objective:
The primary objective of this study is to demonstrate that CNTO 328 in
combination with BSC is superior
to BSC in terms of objective response (complete response [CR] + partial
response [PR]) among subjects
with multicentric Castleman*s disease (MCD).
Secondary Objectives:
The secondary objectives of this study are:
• To demonstrate additional measures of efficacy (duration of tumor response;
time to treatment
failure; change in hemoglobin levels; ability to discontinue corticosteroids;
and improvement in
fatigue, physical function, and other disease-related symptoms)
• To study the safety of prolonged dosing
• To determine the pharmacokinetics of CNTO 328 among subjects with MCD
• To determine a baseline hepcidin value predictive of a >= 2 g/dL increase in
hemoglobin
Study design
This is a A Randomized, Double-blind, Placebo-controlled Study
Intervention
Subjects will receive CNTO 328 (11 mg/kg) or placebo by a 1-hour IV infusion
every 3 weeks. Subjects will be randomly assigned to 2 treatment groups:
• Treatment Group A: Placebo + BSC
• Treatment Group B: CNTO 328 + BSC
Study burden and risks
See page 22 and 23 of the protocol for description of potential risks. Also,
see informed consent for detailed description of all requirements for the
patients.
Antwerpse steenweg 15-17
2340 Beerse
BE
Antwerpse steenweg 15-17
2340 Beerse
BE
Listed location countries
Age
Inclusion criteria
- Measurable and symptomatic MCD proven by biopsy.
- Pretreatment clinical laboratory values meeting these criteria within 4 weeks before treatment:
a. Absolute neutrophil count (ANC) >= 1.0 x 109/L
b. Platelets >= 75 x 109/L
c. ALT within 2.5 x ULN; total bilirubin within 2.5 x ULN; unfractionated alkaline phosphatase within
2.5 x ULN; if unfractionated alkaline phosphatase is above 2.5 x ULN, subjects will be eligible if alkaline phosphatase liver fraction is within 2.5 x ULN
d. Serum creatinine <= 3.0 mg/dL
- ECOG Performance Status of 0, 1, or 2
- Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone (or equivalent, and has remained stable or decreased over the 4 weeks before
enrollment
Exclusion criteria
1. HIV or HHV-8 positive
2. Previous lymphoma
3. Malignancies
4. Concurrent medical condition or disease that is likely to interfere with study procedures or results
5. Use of disallowed therapies: other concomitant anti-tumor therapies for Castleman*s disease
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012380-34-NL |
| CCMO | NL29786.078.09 |