Tocilizumab for KSHV-Associated Multicentric Castleman Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01441063
• Date of registration: 24/09/2011
• Prospective Registration: No
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Tocilizumab for KSHV-Associated Multicentric Castleman Disease
• Scientific title: Pilot Study of Tocilizumab in Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV) - Associated Multicentric Castleman Disease
• Date of first enrolment: September 13, 2011
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01441063
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Robert Yarchoan, M.D.
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion criteria

- 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]
- Thrombocytopenia (
- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Giant Lymph Node Hyperplasia

Castleman Disease

Multicentric Castleman Disease

Intervention(s)

Drug: Tocilizumab

Drug: Valganciclovir (VGC)

Drug: Zidovudine

Primary Outcome(s)

Percentage of Participants With an Overall Clinical Benefit Response [Time Frame: every 2 weeks for up to 12 weeks]

Secondary Outcome(s)

Percentage of Participants With a Radiographic Response [Time Frame: up to 12 weeks]

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.]

Percentage of Participants With Overall Survival 4 Months After Treatment With Tocilizumab and Tocilizumab /Zidovudine (AZT)/Valganciclovir (VGC) [Time Frame: 4 months]

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.]

Percentage of Participants With [Time Frame: each cycle, up to 6 years, 8 months and 24 days.]

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.]

Percentage of Participants With a Biochemical Response [Time Frame: up to 12 weeks]

Percentage of Participants With a Clinical Response [Time Frame: up to 12 weeks]

Percentage of Participants With Grade 3 or Greater Serious Adverse Events [Time Frame: each cycle, up to 6 years, 8 months and 24 days.]

Effect of Tocilizumab on the Pharmacokinetics (PK) of Antiretroviral Agents [Time Frame: Cycle 1, Day 1 and Cycle 2-6 Day 1]

Percentage of Participants Progression-free Survival at 4 Months [Time Frame: 4 months]

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.]

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.]

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.]

Secondary ID(s)

11-C-0233

110233

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/06/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01441063