Multicentric Castleman DiseasePhase 2NCT04585893
Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi
A Phase 2 study testing Rituximab and Etoposide in people with Multicentric Castleman Disease, run by UNC Lineberger Comprehensive Cancer Center at 1 site in Malawi.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multicentric Castleman Disease
- What is being tested?
- Rituximab and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteMalawi
- Study dates
- 22 Jun 2021to 7 Jun 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Females of childbearing potential must have a negative urine pregnancy test within three days prior to registration.
- NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
- Females must agree to abstain from breastfeeding during therapy and for 6 months after the completion of therapy.
- Females of childbearing potential must be willing to abstain from heterosexual activity or to use two forms of effective methods of contraception from the time of informed consent until 12 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, a barrier method plus a hormonal method, or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label.
- Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 6 months after the last dose of study therapy.
- More than 7 days without corticosteroid use prior to starting the treatment.
Who cannot join
- 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.
- If HIV negative and a) hepatitis B virus surface antigen positive or b) a combination of HepB core antibody positive and HepB surface antibody negative (indicative of chronic infection) unless on tenofovir or lamivudine. All HIV-infected patients must be on tenofovir or lamivudine as part of the inclusion criteria.
- Active infection requiring systemic therapy.
- Treatment with any investigational drug within 28 days prior to registration.
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: LCCC 1950 - Rituximab for Multicentric Castleman Disease in Malawi, A Single-Arm Phase II Safety/Efficacy Trial
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.
Read the detailed description
This study aims to determine the safety and efficacy of first-line, risk-stratified rituximab-based MCD treatment in Malawi in a single-arm, phase II clinical trial. The investigators will enroll 27 subjects with newly diagnosed or previously treated MCD (who have not previously received rituximab) requiring treatment (B symptoms or hemoglobin <10 g/dL). Subjects will be treated with four weekly doses of rituximab. High-risk subjects (defined as patients with Eastern Cooperative Oncology Group (ECOG) performance status >2 or hemoglobin <8 g/dL) will also receive etoposide chemotherapy. Subjects will be followed for one year for toxicity and two years for survival. The primary outcome will be safety, defined as the frequency of ≥Grade 3 treatment-related Common Terminology Criteria for Adverse Events (AEs). Secondary outcomes will be event-free survival (death, progression, or development of NHL) and 1- and 2-year overall survival (OS). The investigators also aim to compare the cost-effectiveness of first-line rituximab treatment for MCD in Malawi to chemotherapy (using the investigators' historical controls).
- Conditions
- Multicentric Castleman Disease
- Keywords
- Multicentric Castleman Disease, MCD, HIV, Rituximab, single arm phase 2, safety and efficacy
- Medical subject headings
- Multi-centric Castleman's Disease, Macular dystrophy, corneal type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
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.
EtoposideDrug
Also called Toposar, VP-16
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Rituximab; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From the start of rituximab-based therapy to 12 weeks. (Up to 13 weeks)
Secondary outcomes (13)
Characterization of MCD Presentation in Malawi
Characterization of Multicentric Castleman disease (MCD) presentation in Malawi will be summarized using baseline demographics and laboratory values. Descriptive statistics will be performed.
Measured: Baseline - until 21 days
Overall Survival
Overall survival is the measure of time from the first treatment day to the date of death for any cause. Subjects who have not had an event will be censored at the date of the last assessment documenting the subject was alive.
Measured: 90 days, 1 year, and 2 years
Event-free Survival
Event-free survival is the measure of time after treatment during which no sign of cancer (refractory disease, relapse, non-Hodgkin lymphoma development, or death ) is found.
Measured: 90 days, 1 year, and 2 years
Efficacy of Risk-adjusted Treatment
The efficacy of risk-adjusted treatment will be defined as the clinical response rate which is the resolution of presenting signs/symptoms that defined the Multicentric Castleman disease (MCD) attack. MCD attack/flare is defined as the presence of each of the following three criteria: 1) Fever (subjective or objective), 2) Lymphadenopathy or hepatosplenomegaly, 3) At least one of the following signs or symptoms attributable to MCD by the local study investigator: a) Weight loss >5%, b) Malaise, c) Anemia (Hemoglobin <10 g/dL), and d) Thrombocytopenia (Platelets <100 x 10^3/uL).
Measured: At the end of the treatment, 12 weeks after start of the treatment
Clinical Response Rate
Clinical Response Rate will be defined as the percentage of subjects who achieved resolution of presenting signs/symptoms that defined the Multicentric Castleman disease (MCD) attack) without relapse.
Measured: At the end of the treatment, 12 weeks after start of the treatment
Radiological Response Rate
The Radiological Response Rate will be defined as the percentage of subjects without relapse defined using chest radiography, abdominal sonography, and physical exam for gross lymphadenopathy.
Response criteria for lymph node response will be Complete response (CR)- the disappearance of all evident disease; Partial response (PR)-at least a 50% decrease in target lesions with no increase in non-target lesions, Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD); PD- the appearance of a new lesion or at least a 50% increase in lesion size.
Measured: At the end of the treatment, 12 weeks after start of the treatment
Additional Safety
Additional Safety will be defined as all Adverse Events occurred. AEs will be evaluated using National Cancer Institute's Common Terminology Criteria for Adverse Events version 5 (CTCAE v5).
Measured: First day of the treatment through 12 weeks (Up to 13 weeks)
The Rate of Kaposi Sarcoma Exacerbation
The rate of Kaposi sarcoma exacerbation will be determined by symptomatic or clinical (dermatologic or visceral organ) exacerbation of the disease. All disease flares will be biopsy confirmed whenever possible.
Measured: Up to 2 years
Quality of Life- Patient-reported Outcomes Questionnaires
Quality of Life- patient-reported outcomes (PRO) questionnaires will be assessed by the Patient-Reported Outcomes Measurement Information System Global Health Survey (PROMIS Global-10). The survey includes 10 items about mental and physical health rated on Likert scales ranging from 1 to 5, with higher scores indicative of better health.
Measured: Baseline, week3, end of the treatment, 12 weeks, 6 months after the treatment, 24 months after the treatment, time of relapse.
Change in Hemoglobin Measurement
Hemoglobin will be measured in grams per deciliter (g/dL) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.
Measured: Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in Platelet Count Measurement
Platelet count will be measured in microliters (µl) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.
Measured: Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in C-reactive Protein Measurement
C-reactive protein (CRP) will be measured in milligrams per milliliter (mg/mL) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.
Measured: Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in Kaposi Sarcoma Herpesvirus Viral Load Measurement
Kaposi sarcoma herpesvirus (KSHV) viral load will be measured in copies per milliliter (copies/mL) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.
Measured: Baseline, Day 15 and End of treatment (approximately 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start22 Jun 2021
- Primary completion30 Aug 2024
- Study completion7 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multicentric Castleman DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Fogarty International Center of the National Institute of Health
- Responsible party
- Sponsor
- Investigators
- Yuri Fedoriw, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04585893
- Sponsor's protocol ID
- LCCC 1950
- Other IDs
- K01TW011470
- Status last verified
- Jul 2026
- First submitted
- 10 Sep 2020
- Last updated
- 30 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No