A Phase 2 interventional study of Rituximab and Etoposide in Multicentric Castleman Disease, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 1 site in Malawi. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-30.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
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.
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).
UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 414 studies on the registry; 96 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 25 (78%) have results posted.
Counted across the registry records on this site, refreshed daily.
MCD treatment indicated based on the presence of a symptomatic MCD flare, defined as the presence of each of the following three criteria:
At least one of the following signs or symptoms attributable to MCD by the local study investigator:
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.
Exclusion Criteria:
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
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
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
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).
Time frame: From the start of rituximab-based therapy to 12 weeks. (Up to 13 weeks)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Day 15 and End of treatment (approximately 6 weeks)
Participants were recruited from 06/22/2021 through 06/07/2024 at one center in Malawi.
| Milestone | High-risk Patients | Low-risk Patients |
|---|---|---|
| Started | 9 | 6 |
| Completed | 8 | 6 |
| Not completed | 1 | 0 |
| Withdrew: Death | 1 | 0 |
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).
| Participants | High-risk Patients | Low-risk Patients |
|---|---|---|
| Number of Participant With Non-hematologic Grade ≥3 Adverse Events (AEs) | 0 | 0 |
Characterization of Multicentric Castleman disease (MCD) presentation in Malawi will be summarized using baseline demographics and laboratory values. Descriptive statistics will be performed.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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).
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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).
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
Platelet count will be measured in microliters (µl) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
Collected over Up to 12 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High-risk Patients | 1/9 (11.1%) | 1/9 (11.1%) | 9/9 (100%) |
| Low-risk Patients | 0/6 (0%) | 1/6 (16.7%) | 6/6 (100%) |
| Event | High-risk Patients | Low-risk Patients |
|---|---|---|
| neutrophil count decreasedBlood and lymphatic system disorders | 0/9 | 1/6 |
| AnemiaBlood and lymphatic system disorders | 1/9 | 0/6 |
| Event | High-risk Patients | Low-risk Patients |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 8/9 | 5/6 |
| Lymphocyte count decreasedInvestigations | 7/9 | 1/6 |
| Neutrophil count decreasedInvestigations | 5/9 | 1/6 |
| Lung infectionInfections and infestations | 4/9 | 0/6 |
| Blood lactate dehydrogenase increasedInvestigations | 4/9 | 0/6 |
| Creatinine increasedInvestigations | 3/9 | 1/6 |
| HypoalbuminemiaInvestigations | 3/9 | 2/6 |
| Abdominal painGastrointestinal disorders | 2/9 | 0/6 |
| Non-cardiac chest painGeneral disorders | 2/9 | 0/6 |
| HypotensionVascular disorders | 2/9 | 0/6 |
| Age, Continuous(years) | High-risk Patients | Low-risk Patients | Total |
|---|---|---|---|
| Mean | 40.44 ± 11.13 | 38.66 ± 8.23 | 39.73 ± 9.79 |
| Sex: Female, Male(Participants) | High-risk Patients | Low-risk Patients | Total |
|---|---|---|---|
| Female | 3 | 2 | 5 |
| Male | 6 | 4 | 10 |
| Ethnicity (NIH/OMB)(Participants) | High-risk Patients | Low-risk Patients | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 9 | 6 | 15 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | High-risk Patients | Low-risk Patients | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 9 | 6 | 15 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | High-risk Patients | Low-risk Patients | Total |
|---|---|---|---|
| Malawi | 9 | 6 | 15 |
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Multi-centric Castleman's Disease
UNC Lineberger Comprehensive Cancer Center