Trial Outcomes & Findings for Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi (NCT NCT04585893)

Last Updated: 2025-09-11

Results Overview

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).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

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

Results posted on

2025-09-11

Participant Flow

Participants were recruited from 06/22/2021 through 06/07/2024 at one center in Malawi.

Fifteen subjects were enrolled in the study between 06/22/2021 and 06/07/2024.

Participant milestones

Participant milestones
Measure	High-risk Patients 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 Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
Overall Study STARTED	9	6
Overall Study COMPLETED	8	6
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	High-risk Patients 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 Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-risk Patients n=9 Participants 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 n=6 Participants Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.	Total n=15 Participants Total of all reporting groups
Age, Continuous	40.44 years STANDARD_DEVIATION 11.13 • n=5 Participants	38.66 years STANDARD_DEVIATION 8.23 • n=7 Participants	39.73 years STANDARD_DEVIATION 9.79 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Malawi	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

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

Population: All participants started the study.

Outcome measures

Outcome measures
Measure	High-risk Patients n=9 Participants 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 n=6 Participants Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
Number of Participant With Non-hematologic Grade ≥3 Adverse Events (AEs)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline - until 21 days

Characterization of Multicentric Castleman disease (MCD) presentation in Malawi will be summarized using baseline demographics and laboratory values. Descriptive statistics will be performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 90 days, 1 year, and 2 years

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 90 days, 1 year, and 2 years

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At the end of the treatment, 12 weeks after start of the 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First day of the treatment through 12 weeks (Up to 13 weeks)

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, week3, end of the treatment, 12 weeks, 6 months after the treatment, 24 months after the treatment, time of relapse.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 15 and End of treatment (approximately 6 weeks)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 15 and End of treatment (approximately 6 weeks)

Platelet count will be measured in microliters (µl) at baseline, day 15, and end-of-treatment. Differences will be compared by paired t-test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 15 and End of treatment (approximately 6 weeks)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 15 and End of treatment (approximately 6 weeks)

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.

Outcome measures

Outcome data not reported

Adverse Events

High-risk Patients

Serious events: 1 serious events

Other events: 9 other events

Deaths: 1 deaths

Low-risk Patients

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	High-risk Patients n=9 participants at risk 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 n=6 participants at risk Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
Blood and lymphatic system disorders Anemia	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Blood and lymphatic system disorders neutrophil count decreased	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.

Other adverse events

Additional Information

Matthew S Painschab

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-4431

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	High-risk Patients n=9 participants at risk 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 n=6 participants at risk Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
Blood and lymphatic system disorders Anemia	88.9% 8/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	83.3% 5/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Gastrointestinal disorders Abdominal pain	22.2% 2/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
General disorders Flu like symptoms	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
General disorders Non-cardiac chest pain	22.2% 2/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Infections and infestations Lung infection	44.4% 4/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Blood bilirubin increased	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Blood lactate dehydrogenase increased	44.4% 4/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Creatinine increased	33.3% 3/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Lymphocyte count decreased	77.8% 7/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Neutrophil count decreased	55.6% 5/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Hypoalbuminemia	33.3% 3/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	33.3% 2/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Vascular disorders Hypotension	22.2% 2/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Alkaline Phosphatase Increased	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Investigations Aspartate Aminotransferase Increased	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Injury, poisoning and procedural complications Bruising	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Nervous system disorders Dysgeusia	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
General disorders Fever	22.2% 2/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Vascular disorders Hypertension	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal Inflammation	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Nervous system disorders Neuralgia	0.00% 0/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Nervous system disorders Peripheral Sensory Neuropathy	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Infections and infestations Pharyngitis	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Blood and lymphatic system disorders Platelet count decreased	22.2% 2/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	16.7% 1/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Infections and infestations Urinary Tract Infection	11.1% 1/9 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.	0.00% 0/6 • Up to 12 weeks Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.