Natural History of KSHV-Associated Multicentric Castleman s Disease

NCT ID: NCT04968288

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

195 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-11-17

Study Completion Date

2035-01-01

Brief Summary

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Background:

Kaposi s sarcoma herpes virus (KSHV) causes several kinds of cancer, Kaposi sarcoma (KS), a form of Multicentric Castleman s Disease (MCD) and a type of lymphoma known as Primary Effusion Lymphoma (PEL). These cancers can occur alone or at the same time in the same patient. MCD can cause a lot of symptoms and problems with various organs in the body, making patients feel quite unwell. If unrecognized, the disease can be fatal. Medications such as rituximab alone or in combination with chemotherapy may help treat MCD but there is little known about the long term effects and the natural course of MCD.

Objective:

To better understand the biology of KSHV-MCD to help identify how this disease causes illness and how cancer treatments known to be effective in MCD may help patients with this condition. This study also aims to help identify ways to treat the disease by providing other standard cancer treatments that would be useful to use to treat MCD based on what we know about this condition.

Eligibility:

People 18 years of age and older with KSHV-MCD.

Design:

Participants will be screened with:

Medical history

Physical exam

CT scan

Blood and heart tests

Participants will have an initial evaluation. This will include:

Review of participants symptoms and ability to perform their normal activities

Blood and urine tests

Imaging studies such as CT and PET scans. Participants may have a contrast agent injected into their arm.

Photographs to document skin lesions

Optional skin biopsy. For this, a small piece of the skin will be removed.

Optional lymph node needle biopsy

Optional samples of the fluid in the space around the lungs, intestines, or heart

Optional sample of the liquid that surrounds the brain and spinal cord

Saliva samples

DEXA scan to examine the bones

Questionnaires

Optional limb measurements or cognitive tests

Physicians will give participants recommendations about treatment.

After their initial evaluation and any treatment, participants will have additional visits. These will occur every 3 months for the first year, then every 6 months for the second year, and then once a year for up to 1 year.

Detailed Description

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Background:

* Multicentric Castleman s disease (MCD) is a rare but lethal Kaposi s sarcoma-associated herpesvirus (KSHV) associated lymphoproliferative disorder with a historical median survival of 2 years. It occurs more often in HIV-infected individuals than those without HIV infection. The poor prognosis is not fully explained by the underlying HIV, as the HIV-negative cases appear to have little or no survival advantage over the HIV-positive cohort. The disease has no defined standard treatment and there is much to be learned about its pathogenesis and natural history with current treatments.
* Patients with KSHV-MCD may present with other KSHV-associated conditions such as Kaposi sarcoma (KS) and may develop primary effusion lymphoma (PEL) following their diagnosis, which may affect morbidity and mortality. It is not clear how these concurrent conditions develop simultaneously and over time.
* Since 2004, the HIV and AIDS Malignancy Branch (HAMB) has studied the natural history and assessed novel therapies for KSHV-MCD which has contributed to the development of at least two therapies that are now considered as first-line therapies: (1) rituximab plus liposomal doxorubicin and (2) high dose zidovudine plus valganciclovir.
* These therapies plus either rituximab alone or other rituximab-based therapies that have been developed over the last 15 years have resulted in durable responses in patients with KSHV-MCD and have substantially improved the prognosis of these patients.
* The longitudinal evaluations along with tissue sample collection, imaging studies, and participant reported outcomes will allow for the development of a better understanding of the natural history of this disease, and the development of the basis for more effective treatments.

Objective:

-To study and describe the natural history of KSHV-MCD

Eligibility:

* Age \>= 18 years
* Biopsy proven KSHV-associated MCD

Design:

* This will be a long-term study to comprehensively study participants with KSHV-MCD
* Medical history will be collected, and participants followed throughout the course of their illness, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, and duration of responses
* Tissue samples and blood will be obtained from participants during this study.
* We anticipate accruing 135 evaluable participants on this protocol

Conditions

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Multicentric Castleman s Disease

Keywords

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Kaposi s sarcoma HIV primary effusion lymphoma interlerleukin-6 Natural History

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

Subjects with KSHV-associated MCD

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Biopsy proven KSHV-associated MCD, confirmed in the Laboratory of Pathology (LP), CCR
* Age \>=18 years.
* ECOG performance status \<=4 (Karnofsky \>=20%).
* Ability of subject to understand and the willingness to sign a written informed consent document.
* Participants may be co-enrolled in other protocols, including investigational studies to treat KSHV-associated malignancies.

Exclusion Criteria

* Any condition or set of circumstances that in the opinion of the investigators would make participation in this study unsafe or otherwise inappropriate for a given individual.
* Pregnancy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ramya M Ramaswami, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Irene B Ekwede, R.N.

Role: CONTACT

Phone: (240) 760-6126

Email: [email protected]

Ramya M Ramaswami, M.D.

Role: CONTACT

Phone: (240) 506-1088

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Role: primary

Related Links

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Other Identifiers

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000337-C

Identifier Type: -

Identifier Source: secondary_id

10000337

Identifier Type: -

Identifier Source: org_study_id