Phase 2
N=8
Tocilizumab for KSHV-Associated Multicentric Castleman Disease
Castleman Disease · Multicentric Castleman Disease · Giant Lymph Node Hyperplasia
Bottom Line
View on ClinicalTrials.gov: NCT01441063 ↗Enrolled (actual)
8
Serious AEs
9.1%
Results posted
Jun 2020
Primary outcome: Primary: Percentage of Participants With an Overall Clinical Benefit Response — 63; 100; 50; 67 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Zidovudine (Drug); Tocilizumab (Drug); Valganciclovir (VGC) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With an Overall Clinical Benefit Response |
63; 100; 50; 67; 13; 33 | — |
| SECONDARY Percentage of Participants With a Clinical Response |
75; 100; 25; 33; 0; 0 | — |
| SECONDARY Percentage of Participants With a Biochemical Response |
50; 100; 13; 67; 38; 33 | — |
| SECONDARY Percentage of Participants With a Radiographic Response |
13; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Kaposi Sarcoma Responses Per the Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Response Criteria |
0; 0; 0; 0; 100; 0 | — |
| SECONDARY Changes in Plasma Exposure of Ritonavir in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) |
— | — |
| SECONDARY Changes in Plasma Exposure of Lopinavir in Response to Tocilizumab and AZT Metabolized by Cytochrome P450 (CYP450) |
— | — |
| SECONDARY Changes in Plasma Exposure of Atazanavir in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) |
— | — |
| SECONDARY Changes in Plasma Exposure of Efavirenz in Response to Tocilizumab and Zidovudine (AZT) Metabolized by Cytochrome P450 (CYP450) |
— | — |
| SECONDARY Percentage of Participants With Grade 3 or Greater Serious Adverse Events |
25; 67 | — |
| SECONDARY Percentage of Participants With <Grade 3 Non- Serious Adverse Events |
100; 100; 100; 100; 63; 100 | — |
| SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
8; 3 | — |
| SECONDARY Effect of Tocilizumab on the Pharmacokinetics (PK) of Antiretroviral Agents |
— | — |
| SECONDARY Percentage of Participants Progression-free Survival at 4 Months |
25; 33 | — |
| SECONDARY Percentage of Participants With Overall Survival 4 Months After Treatment With Tocilizumab and Tocilizumab /Zidovudine (AZT)/Valganciclovir (VGC) |
100; 100 | — |
Summary
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.
Eligibility 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] 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
Data sourced from ClinicalTrials.gov (NCT01441063). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.