Tocilizumab for KSHV-Associated Multicentric Castleman Disease
National Cancer Institute (NCI)
Information provided by (Responsible Party)
National Institutes of Health Clinical Center (CC)
First received: September 24, 2011
Last updated: March 3, 2020
Last Verified: January 8, 2020
History of Changes
- KSHV-associated multicentric Castleman disease (KSHV-MCD) is caused by a herpes virus known as KSHV. This disease can also cause several other cancers, including Kaposi sarcoma. People with KSHV-MCD often have symptoms like fever, weight and muscle loss, and fluid in the legs or abdomen. Tocilizumab may be able to block the chemicals in the body that cause KSHV-MCD symptoms. Researchers want to test this drug and other anti-virus drugs to find the best combination of drugs to treat KSHV-MCD.
- To test the effectiveness of tocilizumab with and without other anti-virus drugs for KSHV-MCD.
- People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood abnormalities caused by their KSHV-MCD.
- Participants will be screened with a medical history and physical exam. They will also have blood tests, and a skin biopsy.
- Participants will have tocilizumab injections every 2 weeks for up to 12 weeks. They will provide daily blood samples for the first 3 days of treatment.
- After the sixth dose, participants will be monitored for 4 weeks to check for possible side effects.
- Those whose KSHV-MCD does not improve or worsens during the study may have tocilizumab combined with two other anti-virus drugs, zidovudine and valganciclovir. These drugs are pills that will be taken four times a day for 5 days out of every 2 weeks.
Giant Lymph Node Hyperplasia
Drug : Zidovudine
Drug : Tocilizumab
Drug : Valganciclovir (VGC)
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Pilot Study of Tocilizumab in Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV) - Associated Multicentric Castleman Disease|
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures
Determine the efficacy of tocilizumab in the treatment of KSHV-MCD.
[ Time Frame: every 2 weeks for up to 12 weeks ]
Evaluation of MCD clinical and biochemical response at each visit using a modified KSHV- MCD Clinical Benefit Response Criteria.
- Best clinical, biochemical, radiographic, and overall response
[ Time Frame: up to 12 weeks ]
Evaluate best clinical, biochemical, radiographic, and overall response in patients with KSHV- associated MCD treated for up to 12 weekswith tocilizumab 8mg/kg every 2 weeks using the prior NCI KSHV-MCD Response Criteria
- Effect of tocilizumab + AZT
[ Time Frame: days 1-5 of a 14-day cycle ]
Explore preliminarily the activity of tocilizumab 8mg/kg every 2 weeks, combined with AZT 600 mg orally q6 hours and VGC 900 mg orally q12 hours in patients with inadequate response to tocilizumab monotherapy
- Safety and tolerability
[ Time Frame: each cycle ]
Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC in patients with inadequate response to tocilizumabmonotherapy
- Effect of tocilizumab on the PK of antiretroviral agents
[ Time Frame: C1D1, C2-6 D1 ]
Evaluate the effect of tocilizumab on the pharmacokinetics ofantiretroviral agents that are CYP3A4 substrates in patients with symptomatic KSHV-MCD
- Effect of tocilizumab on KS
[ Time Frame: Baseline, week 7, and at offstudy visit ]
Evaluate the best KS response, using modified ACTG Response criteria in patients with concurrent Kaposi sarcoma
- Progression-free and overall survival
[ Time Frame: 4 months ]
Evaluate progression-free and overall survival with tocilizumab and tocilizumab /AZT/VGC
|Study Start Date:||September 13, 2011|
|Estimated Study Completion Date:||July 1, 2023|
|Estimated Primary Completion Date:||June 6, 2018 (Final data collection date for primary outcome measure)|
Tocilizumab 8 mg/kg on Day 1 of a 14 day cycle a maximum of 6 cycles. If indicated, AZT and VGC will be administered concurrently with toclizumab, with day 1 of the cycle being the day toclizumab is administered.
Zidovudine (AZT) 600 mg orally q6 hours (every 6 hours)
Tocilizumab 8mg/kg every 2 weeks
Drug: Valganciclovir (VGC)
Valganciclovir (VGC) 900 mg orally q12 hours (every 12 hours) on days 1-5 of a 14-day cycle.
- Kaposi sarcoma herpesvirus-associated multicentric Castleman disease (KSHVMCD) is a rare lymphoproliferative disorder that develops predominantly in HIVinfected patients. Patients often have symptoms from interleukin-6 (IL-6), KSHVencoded viral IL-6 (vIL-6), and other cytokines
- Goals of therapy include rapid resolution symptoms and elimination of reservoirs of KSHV-infected plasmablasts.
- Tocilizumab is a humanized anti-IL-6 receptor (gp80) antibody with activity against MCD unrelated to KSHV (KSHV-negative MCD). While tocilizumab does not directly affect vIL-6 signaling or other KSHV driven pathologic processes, IL-6 overproduction plays a major role in symptoms in KSHV-MCD, and blocking IL-6 may be sufficient to treat this disorder by blocking autocrine and paracrine stimulation. Combination with zidovudine (AZT) and valganciclovir (VGC), agents that target KSHV replication, have virus-activated cytotoxic activity, and are active in KSHV-MCD may be useful and necessary in some patients.
- Estimate best clinical, biochemical, radiographic, and overall responses in patients with KSHV-MCD treated for up to 12 weeks with tocilizumab 8mg/kg every 2 weeks using the prior NCI KSHV-MCD Response Criteria.
- In patients with inadequate response to tocilizumab monotherapy: explore preliminarily the activity of tocilizumab 8mg/kg every 2 weeks, combined with AZT 600 mg orally q6 hours and VGC 900 mg orally q12 hours on days 1-5 of a 14-day cycle
- Evaluate safety and tolerability of tocilizumab alone and combined with AZT/VGC
- Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are CYP3A4 substrates in patients with symptomatic KSHV-MCD
- Evaluate progression-free and overall survival of patients treated with tocilizumab and tocilizumab/AZT/VGC
- Evaluate of effect of tocilizumab on KS
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
- Pathologically confirmed KSHV-MCD
- Age greater than or equal to 18
- At least one clinical symptom probably or definitely attributed to KSHV-MCD
- Intermittent or persistent fever for at least 1 week (>38 degrees C)
- Fatigue (CTCAE Grade 2 or greater)
- Gastrointestinal symptoms [includes nausea and anorexia] (CTCAE Grade 1 or greater)
- Respiratory symptoms [includes cough and airway hyperreactivity]
- At least one laboratory abnormality probably or definitely attributed to KSHVMCD
- Anemia (Hgb [men] =12.5 gm/dL, Hgb [women] = 11 gm/dL)
- Thrombocytopenia (=130,000/mm(3))
- Hypoalbuminemia (<3.4 g/dl)
- Elevated C-reactive protein (CRP) (CRP > 3 mg/L)] probably or definitely attributable to KSHV-MCD
- No life- or organ-threatening manifestations of MCD
- ECOG performance status less than or equal to 2
- HIV-infected patients should be receiving or willing to initiate an effective combination antiretroviral therapy (cART) regimen
- Willingness to complete tuberculosis evaluation and start prophylactic antituberculosis therapy as soon as is medically feasible if patients have a reactive tuberculin skin test and have not completed an adequate course of prevented anti-tuberculosis therapy, following American Thoracic Society / Centers for
(CTCAE Grade 1 or greater)
Disease Control recommended guidelines:
- Uncontrolled bacterial, mycobacterial, or fungal infection
- Uncontrolled intercurrent illness including, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or ability to receive therapy.
- Pregnant or lactating women
- Any abnormality that would be scored as NCI CTC Grade 3 toxicity that is unrelated to HIV, its treatment, or to MCD that would preclude protocol treatment. Exceptions include:
- Direct manifestations of Kaposi sarcoma or MCD
- Direct manifestation of HIV (i.e. low CD4 count)
- Direct manifestation of HIV therapy (i.e. Hyperbilirubinemia associated with protease inhibitors)
- Asymptomatic hyperuricemia
- Elevated CK attributed to exercise
- Past or present history of malignant tumors other than Kaposi sarcoma unless one of the following:
- Complete remission for greater than or equal to 1 year from completion of therapy
- Completely resected basal cell carcinoma
- In situ squamous cell carcinoma of the cervix or anus
- Patients with concurrent Kaposi sarcoma requiring immediate cytotoxic chemotherapy
- History of tocilizumab therapy within prior three months
- History of rituximab or bevacizumab therapy within three months
- History of greater than or equal to 2 allergic reaction or any grade anaphylactic
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441063
Locations Show More
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
Sponsors and CollaboratorsNational Cancer Institute (NCI)
|Principal Investigator:||Robert Yarchoan, M.D.||National Cancer Institute (NCI)|
Additional Information:NIH Clinical Center Detailed Web Page
|Responsible Party:||National Cancer Institute (NCI)|
|ClinicalTrials.gov Identifier:||NCT01441063 History of Changes|
|Other Study ID Numbers:||110233|
|Study First Received:||September 24, 2011|
|Last Updated:||March 3, 2020|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Keywords provided by National Institutes of Health Clinical Center (CC):Kaposi Sarcoma Herpesvirus
Human Immunodeficiency Virus
Multicentric Castleman Disease
Additional relevant MeSH terms:
ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.