Tocilizumab for KSHV-Associated Multicentric Castleman Disease
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01441063 |
Recruitment Status :
Completed
First Posted : September 27, 2011
Results First Posted : June 23, 2020
Last Update Posted : October 27, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Background:
- Kaposi's sarcoma-associated herpes virus (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.
Objectives:
- To test the effectiveness of tocilizumab with and without other anti-virus drugs for KSHV-MCD.
Eligibility:
- People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood abnormalities caused by their KSHV-MCD.
Design:
- 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.
- Blood, urine, and saliva samples will be collected throughout the study.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Castleman Disease Multicentric Castleman Disease Giant Lymph Node Hyperplasia | Drug: Zidovudine Drug: Tocilizumab Drug: Valganciclovir (VGC) | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 8 participants |
Allocation: | N/A |
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 |
Actual Study Start Date : | September 13, 2011 |
Actual Primary Completion Date : | June 6, 2018 |
Actual Study Completion Date : | October 5, 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Tocilizumab
Tocilizumab 8 mg/kg on Day 1 of a 14 day cycle a maximum of 6 cycles. If indicated, zidovudine (AZT) and valganciclovir (VGC) will be administered concurrently with tocilizumab, with day 1 of the cycle being the day tocilizumab is administered.
|
Drug: Zidovudine
Zidovudine (AZT) 600 mg orally q6 hours (every 6 hours)
Other Name: Retrovir Drug: Tocilizumab Tocilizumab 8mg/kg every 2 weeks
Other Name: Actemra Drug: Valganciclovir (VGC) Valganciclovir (VGC) 900 mg orally q12 hours (every 12 hours) on days 1-5 of a 14-day cycle.
Other Name: Valcyte |
- Percentage of Participants With an Overall Clinical Benefit Response [ Time Frame: every 2 weeks for up to 12 weeks ]Overall clinical benefit response is defined as Complete Response (CR): Full resolution of all clinical symptoms and laboratory abnormalities (whether or not these are indicator abnormalities) probably or definitely attributable to MCD, lasting at least 3 weeks; and Partial Response (PR): At least 50% of the abnormalities probably or definitely attributed to KSHV-MCD must improve by the minimum amounts specified to attain PR. Only abnormalities present in a specific patient at baseline may count toward the achievement of a PR (e.g. if six of indicator abnormalities are present at baseline, at least three must meet the specified criteria to be considered a PR) assessed using a modified Kaposi sarcoma herpes virus-associated multicentric Castleman disease (KSHV- MCD) Clinical Benefit Response Criteria and the National Cancer Institute (NCI) KSHV-MCD criteria.
- Percentage of Participants With a Clinical Response [ Time Frame: up to 12 weeks ]Clinical response is defined as a Complete Response (CR): Full resolution of all signs and symptoms attributable to MCD, lasting 1 cycle (3-4 weeks depending on regimen; Symptom Free Disease (SFD:) Full resolution of all signs and symptoms attributable to MCD, not yet lasting 1 cycle (3-4 weeks depending on regimen); and Partial Response (PR): Improvement in at least 50% of signs and symptoms by at least 1 grade (NCI-Common Terminology Criteria for Adverse Events (CTCAE v4), with no increased MCD related increases, lasting 1 cycle (3-4 weeks depending on regimen) assessed by the National Cancer Institute Kaposi sarcoma herpes virus-associated multicentric Castleman disease (NCI KSHV-MCD) Response Criteria.
- Percentage of Participants With a Biochemical Response [ Time Frame: up to 12 weeks ]A biochemical response is defined as a Complete Response (CR): Normalization of abnormalities attributed to MCD in the following labs: Complete blood count (CBC), Chem 20, C-Reactive protein (CRP), lasting 1 cycle (3-4 weeks depending on regimen); Partial Response (PR): 50% improvement in all labs abnormalities attributable to MCD, lasting 1 cycle (3-4 weeks depending on regimen), and was assessed by the National Cancer Institute (NCI) Kaposi sarcoma herpes virus-associated multicentric Castleman Disease (KSHV-MCD) Response Criteria.
- Percentage of Participants With a Radiographic Response [ Time Frame: up to 12 weeks ]A radiographic response is defined as a Complete Response (CR): Normalization of all lymph nodes to <1.5 cm in greatest transverse dimension, decrease to < 1 cm of lymph nodes 1.1-1.5 cm at baseline (or 75% decrease in the sum of products of diameters (SPD)), Spleen < 12 cm greatest dimension, no pleural effusions; Complete Response unconfirmed (CRu): Residual lymph node mass >1.5 cm or splenomegaly > 12 cm that has decrease by >75% and does not change over one year; and Partial Response (PR): For lymph nodes, >50% decrease in SPD of 6 dominant nodes, for spleen 50% decrease in longest transverse dimension assessed by the National Cancer Institute (NCI) Kaposi sarcoma herpes virus-associated multicentric Castleman Disease (KSHV-MCD) Response Criteria.
- Percentage of Participants With Kaposi Sarcoma Responses Per the Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Response Criteria [ Time Frame: Baseline, week 7, and at off study visit, approximately 2 weeks following last study treatment for those with KS, up to 14 weeks. ]The ACTG Criteria is defined as a Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), and Symptom Free Disease (SFD). The terms Improved (I), Stable (S), Mixed (M) Response, and Worse (W) are also used to further describe participants who have SD or PR.
- Changes in Plasma Exposure of Ritonavir in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) [ Time Frame: Cycle 1 Day 1: pre Tocilizumab, and 15 minutes, 24 hrs and 48 hrs post drug; Cycle 2-6: pre Tocilizumab dose and 15 minutes post drug dose. ]Cumulative plasma exposure of Ritonavir will be evaluated.
- Changes in Plasma Exposure of Lopinavir in Response to Tocilizumab and AZT Metabolized by Cytochrome P450 (CYP450) [ Time Frame: Cycle 1 Day 1: pre Tocilizumab, and 15 minutes, 24 hrs and 48 hrs post drug; Cycle 2-6: pre Tocilizumab dose and 15 minutes post drug dose. ]Cumulative plasma exposure of Lopinavir will be evaluated.
- Changes in Plasma Exposure of Atazanavir in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) [ Time Frame: Cycle 1 Day 1: pre Tocilizumab, and 15 minutes, 24 hrs and 48 hrs post drug; Cycle 2-6: pre Tocilizumab dose and 15 minutes post drug dose. ]Cumulative plasma exposure of Atazanavir will be evaluated.
- Changes in Plasma Exposure of Efavirenz in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) [ Time Frame: Cycle 1 Day 1: pre Tocilizumab, and 15 minutes, 24 hrs and 48 hrs post drug; Cycle 2-6: pre Tocilizumab dose and 15 minutes post drug dose. ]Cumulative plasma exposure of Efavirenz will be evaluated.
- Percentage of Participants With Grade 3 or Greater Serious Adverse Events [ Time Frame: each cycle, up to 6 years, 8 months and 24 days. ]Here is the percentage of participants with Grade 3 or greater serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe or medically significant, Grade 4 is life threatening, and Grade 5 is death.
- Percentage of Participants With <Grade 3 Non- Serious Adverse Events [ Time Frame: each cycle, up to 6 years, 8 months and 24 days. ]Here is the percentage of participants with <Grade 3 non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. Grade 1 is mild and Grade 2 is moderate.
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 6 years, 8 months and 24 days. ]Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
- Effect of Tocilizumab on the Pharmacokinetics (PK) of Antiretroviral Agents [ Time Frame: Cycle 1, Day 1 and Cycle 2-6 Day 1 ]Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are cytochrome P3A4 (CYP3A4) substrates in patients with symptomatic Kaposi sarcoma herpes virus-associated multicentric Castleman Disease (KSHV-MCD).
- Percentage of Participants Progression-free Survival at 4 Months [ Time Frame: 4 months ]Progression-free survival is defined as participants who progress or die by 4 months after the start of treatment with tocilizumab and tocilizumab /AZT/VGC.
- Percentage of Participants With Overall Survival 4 Months After Treatment With Tocilizumab and Tocilizumab /Zidovudine (AZT)/Valganciclovir (VGC) [ Time Frame: 4 months ]Overall survival is defined as the percentage of participants alive at 4 months after the start of treatment with tocilizumab and tocilizumab /AZT/VGC.

Choosing 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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
- Pathologically confirmed Kaposi sarcoma (KS)-associated herpes virus multi-centric Castleman disease (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 (Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater)
- Gastrointestinal symptoms [includes nausea and anorexia] (CTCAE Grade 1 or greater)
- Respiratory symptoms [includes cough and airway hyperreactivity]
(CTCAE Grade 1 or greater)
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- Human Immunodeficiency Virus (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 Disease Control recommended guidelines:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm
- Ability to understand and willingness to give informed consent
- Women of child bearing potential must agree to use birth control for the duration of the study
EXCLUSION CRITERIA:
- 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 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 3 toxicity that is unrelated to HIV, its treatment, or to MCD that would preclude protocol treatment. Exceptions include:
- Lymphopenia
- Direct manifestations of Kaposi sarcoma or MCD
- Direct manifestation of HIV (i.e. low cluster of differentiation 4 (CD4) count)
- Direct manifestation of HIV therapy (i.e. Hyperbilirubinemia associated with protease inhibitors)
- Asymptomatic hyperuricemia
- Hypophosphatemia
- Elevated creatine kinase (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 reaction during prior administration of tocilizumab

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01441063
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | |
Bethesda, Maryland, United States, 20892 |
Principal Investigator: | Robert Yarchoan, M.D. | National Cancer Institute (NCI) |
Documents provided by Robert Yarchoan, National Cancer Institute (NCI):
Publications of Results:
Other Publications:
Responsible Party: | Robert Yarchoan, Principal Investigator, National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT01441063 |
Other Study ID Numbers: |
110233 11-C-0233 |
First Posted: | September 27, 2011 Key Record Dates |
Results First Posted: | June 23, 2020 |
Last Update Posted: | October 27, 2020 |
Last Verified: | October 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Kaposi Sarcoma Herpesvirus Human Immunodeficiency Virus Tocilizumab Multicentric Castleman Disease |
Interleukin-6 Castleman Disease Acquired Immunodeficiency Syndrome (AIDS) Human Herpesvirus-8 |
Castleman Disease Lymphadenopathy Hyperplasia Pathologic Processes Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Zidovudine Valganciclovir |
Antimetabolites Molecular Mechanisms of Pharmacological Action Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Antiviral Agents Anti-Infective Agents Anti-HIV Agents Anti-Retroviral Agents |