Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi

NCT04585893 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: LCCC 1950K01TW011470
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and efficacy of first-line, risk-stratified Rituximab-based Multicentric Castleman Disease (MCD) treatment in Malawi in a single-arm, phase II clinical trial. This study also aims to compare the cost-effectiveness of first-line Rituximab treatment for MCD in Malawi to chemotherapy.

Conditions

Multicentric Castleman Disease

Keywords

Multicentric Castleman Disease; MCD; HIV; Rituximab; single arm phase 2; safety and efficacy

Outcome Measures

Primary Outcomes (1)

• Number of Participant With Non-hematologic Grade ≥3 Adverse Events (AEs)

  Safety was assessed by the number of participants with non-hematologic Grade ≥3 adverse events (AEs) and treatment-related mortality. AEs were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v5). CTCAE defines AE severity as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), and Grade 5 (death related to AE).

  From the start of rituximab-based therapy to 12 weeks. (Up to 13 weeks)

Secondary Outcomes (13)

• Characterization of MCD Presentation in Malawi

  Baseline - until 21 days

• Overall Survival

  90 days, 1 year, and 2 years

• Event-free Survival

  90 days, 1 year, and 2 years

• Efficacy of Risk-adjusted Treatment

  At the end of the treatment, 12 weeks after start of the treatment

• Clinical Response Rate

  At the end of the treatment, 12 weeks after start of the treatment

Study Arms (1)

Single Arm Rituximab

EXPERIMENTAL

The safety and efficacy of first-line rituximab will be assessed through a risk-stratified rituximab-based Multicentric Castleman disease (MCD) The planned sample size is 27 adult patients accrued at a rate of 10 patients annually. High-risk patients (defined as patients with ECOG performance status \>2 or hemoglobin \<8 g/dL) will receive four weekly doses of rituximab (375 mg/m2) and etoposide (100 mg/m2). Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.

Drug: Rituximab; Drug: Etoposide

Interventions

Rituximab DRUG

375 mg/m\^2 administered via IV infusion weekly for four weeks. Administered via slow IV infusion, starting at 50mg/hr and increasing by 50mg/hr every 30 minutes to a maximum infusion rate of 400mg/hr.

Also known as: Rituxan

Single Arm Rituximab

Etoposide DRUG

Subjects with high-risk disease will receive 100 mg/m\^2 etoposide weekly for four weeks administered over one hour via IV infusion after completion of rituximab

Also known as: Toposar, VP-16

Single Arm Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed or previously treated subjects with KSHV-associated MCD that is pathologically confirmed by characteristic histologic features and latency-associated nuclear antigen (LANA) positivity by Immunohistochemistry (IHC).
• Age is greater than or equal 18 years old at time of consent.
• Can provide informed consent.
• HIV-infected or HIV-uninfected.
• If HIV-infected, must be on or willing to start antiretroviral therapy including lamivudine or tenofovir.
• Willing to comply with study visits.
• MCD treatment indicated based on the presence of a symptomatic MCD flare, defined as the presence of each of the following three criteria:
• Fever (subjective or objective)
• Lymphadenopathy or hepatosplenomegaly
• At least one of the following signs or symptoms attributable to MCD by the local study investigator:
• Weight loss \>5%
• Malaise
• Anemia (Hemoglobin \<10 g/dL) within the past 4 weeks
• Thrombocytopenia (Platelets \<100 x 103/mL) NOTE: If only two of the three criteria are present, but the provider feels treatment is indicated for a symptomatic MCD flare, this will be allowed after communication with the study principal investigator (PI).
• Subjects with low hemoglobin within the past 4 weeks that have since received a blood transfusion are still eligible for participation. The subject's pre-transfusion hemoglobin value will be considered when determining risk classification.

You may not qualify if:

• Symptomatic, extensive-stage KS (T1 by the AIDS Clinical Trials Group (ACTG) staging system; T1 includes ulceration or edema from KS, raised or non-hard palate oral lesions, or any visceral involvement) requiring urgent treatment, to avoid potential rituximab-induced KS worsening.
• Previous rituximab use for MCD.
• Second active malignancy requiring systemic therapy.
• Active infection requiring systemic therapy.
• Treatment with any investigational drug within 28 days prior to registration.
• More than 7 days of corticosteroids immediately prior to enrollment. If the subject is taking corticosteroids for more than 7 days, they require a 7 day washout period before enrollment.
• Bilirubin \>3 mg/dL.
• Creatinine clearance \<30 ml/min by Cockcroft-Gault formula.
• ECOG performance status \>3.
• Pregnant or breastfeeding (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Fogarty International Center of the National Institute of Health: collaborator

Study Sites (1)

UNC Project, Kamuzu Central Hospital

Lilongwe, Malawi

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center Website Homepage

MeSH Terms

Conditions

Multi-centric Castleman's Disease; Macular dystrophy, corneal type 1

Interventions

Rituximab; Etoposide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Matthew S Painschab
• Organization: UNC Lineberger Comprehensive Cancer Center

matthew_painschab@med.unc.edu

919-966-4431

Study Officials

• Matthew Painschab, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: October 14, 2020
• Study Start: June 22, 2021
• Primary Completion: August 30, 2024
• Study Completion (Estimated): June 7, 2026
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-09

Locations

MA (1)