Tocilizumab with or without Zidovudine and Valganciclovir in Treating Patients with Kaposi Sarcoma Herpes Virus-Associated Multicentric Castleman Disease

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Status: Active

Description

This pilot phase II trial studies tocilizumab in treating patients with Kaposi sarcoma herpes virus-associated multicentric Castleman disease. Monoclonal antibodies, such as tocilizumab, can block the ability of cancer to grow and spread. Herpes virus is found in the lesions of most patients with Kaposi's sarcoma and may help cause Kaposi's sarcoma. Zidovudine and valganciclovir are antiviral drugs that act against many types of herpes viruses. Giving tocilizumab with zidovudine and valganciclovir may be an effective treatment for Kaposi's sarcoma herpes virus-associated multicentric Castleman disease.

Eligibility Criteria

Inclusion Criteria

  • Pathologically confirmed KSHV-MCD
  • At least one clinical symptom probably or definitely attributed to KSHV-MCD * Intermittent or persistent fever for at least 1 week (> 38°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 KSHV-MCD * Anemia (hemoglobin [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 =< 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/or positive QuantiFERON-tuberculosis (TB) Gold test and have not completed an adequate course of prevented anti-tuberculosis therapy, following American Thoracic Society/Centers for Disease Control recommended guidelines
  • 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 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 [CD]4 count) * Direct manifestation of HIV therapy (i.e. hyperbilirubinemia associated with protease inhibitors) * Asymptomatic hyperuricemia * Hypophosphatemia * Elevated creatinine kinase (CK) attributed to exercise
  • Past or present history of malignant tumors other than Kaposi sarcoma unless one of the following: * Complete remission for >= 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 6 weeks
  • History of rituximab or intravenous bevacizumab therapy within six weeks
  • History of >= 2 allergic reaction or any grade anaphylactic reaction during prior administration of tocilizumab

Locations & Contacts

Maryland

Bethesda
National Institutes of Health Clinical Center
Status: Active
Contact: Thomas S. Uldrick
Phone: 301-402-6296 Email: uldrickts@mail.nih.gov

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Estimate clinical benefit of tocilizumab 8 mg/kg every 2 weeks for up to 12 weeks in patients with symptomatic Kaposi sarcoma herpes virus-associated multicentric Castleman disease (KSHV-MCD) using a modified KSHV-MCD Clinical Benefit Response Criteria.

SECONDARY OBJECTIVES:

I. Evaluate best clinical, biochemical, radiographic, and overall response in patients with KSHV-associated MCD treated for up to 12 weeks with tocilizumab 8 mg/kg every 2 weeks using the prior National Cancer Institute (NCI) KSHV-MCD Response Criteria.

II. In patients with inadequate response to tocilizumab monotherapy: explore preliminarily the activity of tocilizumab 8 mg/kg every 2 weeks, combined with zidovudine (AZT) 600 mg orally every (q) 6 hours (every 6 hours) and valganciclovir (VGC) 900 mg orally q 12 hours (every 12 hours) on days 1-5 of a 14-day cycle.

III. Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC in this patient population.

IV. Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates in patients with symptomatic KSHV-MCD.

V. Evaluate of effect of therapy on Kaposi sarcoma (KS) using modified acquired immune deficiency syndrome (AIDS) Clinical Trials Group (ACTG) response criteria.

VI. Evaluate progression-free and overall survival with tocilizumab and tocilizumab/AZT/VGC.

OUTLINE:

TOCILIZUMAB ADMINISTRATION: Patients receive tocilizumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

HIGH-DOSE AZT AND VGC ADMINISTRATION: Patients with progressive disease or patients not achieving response by course 4 also receive zidovudine* orally (PO) four times daily (QID) and valganciclovir* PO twice daily (BID) on days 1-5.

*NOTE: Patients not tolerating oral therapy may receive zidovudine IV over 60 minutes QID and valganciclovir IV over 60 minutes BID.

After completion of study treatment, patients are followed up for 4 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
Thomas S. Uldrick

Trial IDs

Primary ID 11-C-0233
Secondary IDs 11C0233, NCI-2013-01504, P10788, 110233
Clinicaltrials.gov ID NCT01441063