Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Castleman Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Unicentric Castleman Disease

Multicentric Castleman Disease

All Drugs and Chemicals

Analgesics

Antipyretics

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Histamine Antagonists

Histamine H1 Antagonists

Immunoglobulins

Siltuximab

Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.

Placebo will be administered as a 1-hour intravenous infusion every 3 weeks + BSC. Participants who do not respond to placebo during the blinded treatment period will have option to crossover and receive siltuximab 11 mg/kg which will be administered by 1-hour intravenous infusion every 3 weeks + BSC during the unblinded treatment period.

Siltuximab 11 mg/kg will be administered by 1-hour intravenous infusion every 3 weeks

Placebo will be administered by 1-hour intravenous infusion every 3 weeks

Placebo

BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.

Best Supportive Care (BSC)

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to demonstrate that CNTO 328 when administered in combination with best supportive care (BSC) is superior to BSC in terms of durable tumor and symptomatic response (complete response or partial response) among patients with Multicentric Castleman's Disease.

This is a multicenter (study conducted at multiple sites), randomized (the study medication is assigned by chance), double blind (neither investigator nor the participant knows the treatment that the participant receives), placebo controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), study to assess the efficacy and safety of CNTO 328 plus BSC compared with BSC in patients with symptomatic Multicentric Castleman's Disease. The study mainly consists of 3 phases, including: the screening phase (majority of assessments performed within 28 days of first dose), the treatment phase (blinded and unblinded), and the follow up phase. In the blinded treatment phase, approximately 78 patients will be randomly assigned in 1:2 ratios to either of 2 treatment groups, ie, Placebo + BSC, or CNTO 328 + BSC. Participants receiving placebo + BSC during blinded treatment period who do not respond and have treatment failure will have the option to crossover and receive siltuximab + BSC during unbllinded treatent period. The follow up phase will be 3 months after last dose of study medication and the survival will be followed up until the study ends. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, patient-recorded temperature, and physical examination will be monitored throughout the study. The total study duration will be 5 years after the last patient starts study medication.

A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease

A Randomized, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of CNTO 328 (Anti IL 6 Monoclonal Antibody) Plus Best Supportive Care Compared With Best Supportive Care in Subjects With Multicentric Castleman's Disease

Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: \>=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Duration of tumor and symptomatic response is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure. Whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions. Symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: \>=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks.

Overall tumor response is CR + PR assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a \>=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Duration of tumor response is defined as time from first documentation of tumor response to tumor progression. Tumour response is complete response (CR) + partial response (PR) as assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a \>=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Time to treatment failure was defined as the time from randomization until the participant fails treatment. Treatment failure was defined as any of the following: a sustained increase from baseline in disease related symptoms \>=Grade 2 persisting for at least 3 weeks despite best supportive care (BSC); onset of any new disease related Grade 3 or higher symptom despite BSC; sustained (ie, at least 3 weeks) deterioration in performance status (increase from baseline in Eastern Cooperative Oncology Group Performance Status by more than 1 point) despite BSC; radiologic progression, as measured by modified Cheson criteria; Initiation of any other therapy intended to treat multicentric Castleman's disease ie, prohibited treatments. Statistical analysis shows difference in treatment failure rate (siltuximab+BSC minus Placebo+BSC).

Hemoglobin response rate is defined as percentage of participants who achieved \>= 15 g/L hemoglobin at Week 13.

Hemoglobin response rate is defined as percentage of participants who achieved \>= 20 g/L hemoglobin at Week 13.

Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).

Overall survival was defined as percent chance of survival of participants who were still alive at 6 years from time of first study treatment was analyzed.

A patient-reported symptom scale. Symptom presence/absence and severity are noted on an anchor-based numeric scale. Scores range from 1 (very mild) to 5 (very severe).

The FACIT-F, a 13-item instrument, was designed to measure patient-reported fatigue. It is one of the suite of FACIT instruments developed for outcomes in cancer. Concepts measured in the scale include tiredness, weakness, and difficulty conducting usual functional activities or social interaction due to fatigue. Response options range from "not at all" (0) to "very much" (4), and yield a summary score. Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.

SF-36 is a questionnaire and PCS is a part of subscale assessing physical functioning, role-physical, bodily pain, and general health. The scores range from 0 (worst score) to 100 (best score), with a higher score indicating better quality of life.

Janssen Research & Development, LLC

Safety Analysis set included all participants who received at least 1 dose of study drug in blinded and unblinded treatment period until 48 weeks after the last subject started study treatment (approximately 3 years). Participants who continued in the study from Week 48 through the end-of-study (5 years after the last participant started study treatment) were included in the Follow-up analysis set.

Participants received placebo as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued or completed treatment period up to Week 48, and who consented to enter the follow-up period were continued to be followed up during the course of follow-up period.

Placebo + Best Supportive Care (BSC) (Blinded)

Participants received siltuximab 11mg/kg as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason completed the end-of-treatment visit and entered the follow-up period.

Siltuximab + Best Supportive Care (BSC) (Blinded)

Participants who had documented treatment failure and wished to continue treatment, their treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab during the unblinded treatment period.

Siltuximab + Best Supportive Care (BSC) (Unblinded)

No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[placebo as a 1 hour IV infusion every 3 weeks along with BSC\]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.

Placebo + BSC (Follow-up Period)

No study treatment was administered during the follow-up period (up to 3 months after last study agent administration \[siltuximab 11mg/kg as a 1 hour IV infusion every 3 weeks along with \]) and participants were followed until death, lost to follow up, withdrawal of consent, death of 50 % of participants, or the end of the study, whichever occurred earlier.

Siltuximab + BSC (Follow-up Period)

Participants received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. If a participant had documented treatment failure and wished to continue treatment, the participant's treatment assignment was unblinded. Upon unblinding placebo participants who received blinded treatment had an option to receive unblinded treatment with siltuximab. Participants who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50% of participants, or end of the study, whichever occurred earlier.

Placebo + Best Supportive Care (BSC)

Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1 hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last participant started study treatment, whichever occurred earlier. Participants who discontinued treatment for any reason, completed End-of-Treatment (EOT) visit and entered Follow-up period. If a participant had documented treatment failure and wished to continue treatment, participant's treatment assignment was unblinded. Upon unblinding, if participant was assigned to siltuximab, study treatment was discontinued, and the participant completed EOT Visit and enter Follow up period (up to 3 months after last study drug intake) wherein participants were followed until death, lost to follow-up, withdrawal of consent, death of 50 percent (%) of participants, or end of the study, whichever occurred earlier.

Siltuximab + Best Supportive Care (BSC)

Total

Age, Continuous

Sex: Female, Male

AUSTRALIA

BELGIUM

BRAZIL

CANADA

CHINA

EGYPT

FRANCE

GERMANY

HONG KONG

ISRAEL

NEW ZEALAND

NORWAY

RUSSIAN FEDERATION

SINGAPORE

SOUTH KOREA

SPAIN

TAIWAN

UNITED KINGDOM

UNITED STATES

Region of Enrollment

DIRECTOR CLINICAL RESEARCH

Null hypothesis: there is no difference in the durable tumor and symptomatic response rate between the 2 treatment arms

Intent-to-treat (ITT) population: all randomized participants.

Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review

All randomized participants who achieved durable tumor and symptomatic response during blinded treatment period as per independent review.

Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review

Response-evaluable Population: included participants who received at least 1 administration of siltuximab/placebo and had at least 1 post-baseline radiologic disease evaluation.

Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review

All randomized participants who achieved tumor response during blinded treatment period as per independent review.

Median Duration of Tumor Response - by Independent Radiology Review

Time to Treatment Failure

Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 postbaseline hemoglobin evaluation.

Percentage of Participants Who Achieved Greater Than or Equal to (>=) 15 Gram Per Liter (g/L) Hemoglobin at Week 13 (Hemoglobin Response Rate)

Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 post-baseline hemoglobin evaluation.

Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)

All randomized participants who were dependent on corticosteroids at baseline.

Percentage of Participants Who Discontinued Corticosteroids

Safety Analysis set included all randomized participants who received at least 1 dose of study agent.

6-year Survival Rate

Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline

Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline

Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline

Blinded Treatment

Unblinded Treatment

Follow-Up Period

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Cardiomyopathies

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Doxorubicin

Liposomal doxorubicin

Lana J Dixon, MB BCh BAO

Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. A retrospective pilot study showed evidence of subclinical dysfunction (including impaired global longitudinal strain) in 42/52 childhood cancer survivors. There is limited research in this area, therefore current guidelines are based on expert opinion alone and lack consensus. Current methods of detection diagnose cardiomyopathy at an irreversible stage i.e. when the compensatory mechanisms are exhausted and the left ventricular ejection fraction impaired. Small trials have shown that early treatment with standard heart failure therapy may reverse damage, further validation is however required in this cohort.

Newer techniques such as tissue doppler and strain rate imaging have shown promise for early prediction of cardiomyopathy in adult studies. Biomarkers such as troponin and NT-proBNP have also shown a correlation with cardiomyopathy.

This study (n=208) aims to use echocardiography, strain imaging, holter monitoring and MRI for early detection of cardiomyopathy. Biomarkers, both currently used (for example, troponin and NTproBNP,) and more novel (for example, IL6, MPO, and sST2) will be assessed to see if early cardiomyopathy can be predicted.

This study will explore biomarker discovery by analysing an age/gender matched subgroup for the top differentially expressed microRNA and protein biomarkers. Selected biomarkers will then be validated in a larger cohort.

CLINICAL APPOINTMENT A linked anonymised Case Report Form will be completed using participant answers and relevant aspects of their electronic care record. This will involve questions about the patient's demographics, chemotherapy history, cardiac symptoms, past medical history, medication history and family history.

Consenting patients will then have

* height, weight and blood pressure taken
* cardiovascular and respiratory examination Participants will then undergo
* SF36 quality of life questionnaire
* 6 minute walk test, grip strength
* Electrocardiogram by a trained researcher
* Venesection- 40ml blood sample from a peripheral vein by the trained researcher Crevicular fluid sample

INVESTIGATIONS

Participants will be invited for:

1. 24 hour holter monitor- arrhythmia assessment
2. Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
3. Magnetic resonance imaging (MRI) scan of the heart- volumetric analysis, late gadolinium enhancement and STIR imaging assessments. As part of the scan the patient will require a venflon to be inserted into a peripheral vein for gadolinium injection. A safety questionnaire will be sent to the patient prior to attendance as part of standard MRI procedure. All safety aspects will be re-assessed on the day of attendance by a trained radiographer

BLOOD SAMPLE ANALYSIS Blood samples will be sent for standard of care and cardiovascular risk assessment. Tests include a full blood picture, urea and electrolytes, C-reactive protein, iron profile, B12 and folate, lipid profile, HbA1c, NT-proBNP and high sensitivity troponin.

Additional disease associated biomarkers for example sST2, MPO, and IL6 will be quantified using immunoassays. Biomarker discovery, including transcriptomics and proteomics will be carried out to identify signatures that could predict cardiotoxicity, subclinical dysfunction, and cardiomyopathy.

Blood samples will be collected for currently used (for example troponin, NTproBNP,) and novel (for example, IL6, MPO, and sST2) biomarkers to see if we can predict early cardiomyopathy. Transcriptomics and proteomics based biomarker discovery will identify new biomarkers to allow timely diagnosis.

Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors

Early Detection of Late Anthracycline Induced Cardiotoxicity in Survivors of Childhood Malignancy

Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines

Levels of high sensitivity troponin T and NT-proBNP

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease	NCT01024036	Multicentric Ca...	Siltuximab Placebo Best Supportive...	18 Years -	Janssen Research & Development, LLC
Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors	NCT04852965	Anthracycline I...		18 Years -	Queen's University, Belfast
A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease	NCT01024036	Multicentric Ca...	Siltuximab Placebo Best Supportive...	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for il6

Every month we try and update this database with for il6 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for il6

Every month we try and update this database with for il6 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for il6 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.