Tocilizumab for KSHV-Associated Multicentric Castleman Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01441063
First received: September 24, 2011
Last updated: March 3, 2015
Last verified: February 2015
  Purpose

Background:

- 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 Intervention Phase
Castleman Disease
Castleman's Disease
Giant Lymph Node Hyperplasia
Drug: Zidovudine
Drug: Tocilizumab
Drug: Valganciclovir (VGC)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Tocilizumab in Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV) - Associated Multicentric Castleman Disease

Resource links provided by NLM:


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: Evaluation of MCD clinical and biochemical response at each visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Estimate best clinical, biochemical, radiographic and overall response. [ Time Frame: Clinical and laboratory responses are assessed in aggregate and compared to baseline. ] [ Designated as safety issue: No ]
  • Evaluate progression-free and overall survival with tocilizumab and tocilizumab/AZT/VGC. [ Time Frame: Time interval from the date of enrollment to the date of progression from best response. ] [ Designated as safety issue: No ]
  • Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC [ Time Frame: Toxicities will be evaluated both per cycle and per patient. ] [ Designated as safety issue: Yes ]
  • Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are CYP3A4 substrates in patients with symptomatic KSHVMCD [ Time Frame: Cycle 1, Day 1, Day 3, Cycles 2--6 ] [ Designated as safety issue: Yes ]
  • Evaluate effect of tocilizumab on KS [ Time Frame: Baseline, week 7 and at off-study ] [ Designated as safety issue: No ]

Estimated Enrollment: 17
Study Start Date: August 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients with KSHV-MCD
Drug: Zidovudine
Zidovudine (AZT) 600 mg orally q6 hours (every 6 hours)
Drug: Tocilizumab
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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]

(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
  • 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

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 NCI 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 CD4 count)
  • Direct manifestation of HIV therapy (i.e. Hyperbilirubinemia associated with protease inhibitors)
  • Asymptomatic hyperuricemia
  • Hypophosphatemia
  • 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 reaction during prior administration of tocilizumab
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441063

Contacts
Contact: Karen Aleman, R.N. (301) 496-8959 alemank@mail.nih.gov
Contact: Thomas S Uldrick, M.D. (301) 402-6296 uldrickts@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas S Uldrick, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01441063     History of Changes
Other Study ID Numbers: 110233, 11-C-0233
Study First Received: September 24, 2011
Last Updated: March 3, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Kaposi Sarcoma Herpesvirus
Human Immunodeficiency Virus
Tocilizumab
Multicentric Castleman Disease
Interleukin-6
Castleman Disease

Additional relevant MeSH terms:
Giant Lymph Node Hyperplasia
Hyperplasia
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Pathologic Processes
Valganciclovir
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015