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

Browse trials for

• Castleman Disease 33

Keywords

• Multicentric Castleman's Disease
• MCD
• CNTO 328
• Best Supportive Care
• Tumor
• Symptomatic response
• Pharmacokinetics
• Interleukin-6
• IL6

Castleman Disease

33 studies on the registry are indexed under Castleman Disease; 10 are open to participants now.

This study's enrollment of 79 is above the median of 25 across 19 interventional studies indexed under Castleman Disease.

Lead sponsor

Janssen Research & Development, LLC is the lead sponsor of 912 studies on the registry; 76 are open to participants now.

Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.

Study arms

• Experimental
  Siltuximab+best supportive care (BSC)

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

  Drug: Siltuximab · Drug: Best Supportive Care (BSC)

• Placebo comparator
  Placebo+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.

  Drug: Placebo · Drug: Best Supportive Care (BSC)

Interventions

• DrugSiltuximab

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

  Also known as: CNTO 328

• DrugPlacebo

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

• DrugBest Supportive Care (BSC)

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

Primary outcomes

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

   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).

   Time frame: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from study, or up to 48 weeks after last participant started study medication(approximately 3 years), whichever occurred earlier

Secondary outcomes

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

   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.

   Time frame: From the date when durable tumour and symptomatic response is achieved until treatment failure, as assessed until 48 weeks after the last participant started study treatment (approximately 3 years)

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

   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).

   Time frame: From Day 1 of Cycle 1 until the date when durable tumour and symptomatic response is achieved, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

3. Median Duration of Tumor Response - by Independent Radiology Review

   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 frame: From the date when tumour response is achieved until tumour progression, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

4. Time to Treatment Failure

   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).

   Time frame: From the date of randomization until a participant fails treatment, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years), whichever occurred earlier

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

   Time frame: Week 13

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

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

   Time frame: Week 13

7. Percentage of Participants Who Discontinued Corticosteroids

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

   Time frame: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years)

8. 6-year Survival Rate

   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.

   Time frame: until 6 years

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

   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).

   Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

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

    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.

    Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

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

    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.

    Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Baseline characteristics

Publications

• van Rhee F, Rosenthal A, Kanhai K, Martin R, Nishimura K, Hoering A, Fajgenbaum DC. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. 2022 Aug 23;6(16):4773-4781. doi: 10.1182/bloodadvances.2022007112. PubMed 35793409 ↗
• Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, Simpson D, Liu AY, Menke D, Chandrakasan S, Lechowicz MJ, Wong RS, Pierson S, Paessler M, Rossi JF, Ide M, Ruth J, Croglio M, Suarez A, Krymskaya V, Chadburn A, Colleoni G, Nasta S, Jayanthan R, Nabel CS, Casper C, Dispenzieri A, Fossa A, Kelleher D, Kurzrock R, Voorhees P, Dogan A, Yoshizaki K, van Rhee F, Oksenhendler E, Jaffe ES, Elenitoba-Johnson KS, Lim MS. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017 Mar 23;129(12):1646-1657. doi: 10.1182/blood-2016-10-746933. Epub 2017 Jan 13. PubMed 28087540 ↗
• van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, Simpson D, Capra M, Liu T, Hsieh RK, Goh YT, Zhu J, Cho SG, Ren H, Cavet J, Bandekar R, Rothman M, Puchalski TA, Reddy M, van de Velde H, Vermeulen J, Casper C. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014 Aug;15(9):966-74. doi: 10.1016/S1470-2045(14)70319-5. Epub 2014 Jul 17. Erratum In: Lancet Oncol. 2014 Sep;15(10):417. PubMed 25042199 ↗