Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| K01TW011470 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Fogarty International Center of the National Institute of Health | NIH |
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline - until 21 days |
| Overall Survival |
Not provided
Inclusion Criteria:
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:
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.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Matthew Painschab, MD | University of North Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Project, Kamuzu Central Hospital | Lilongwe | Malawi |
Not provided
| Label | URL |
|---|---|
| UNC Lineberger Comprehensive Cancer Center Website Homepage | View source |
Not provided
Fifteen subjects were enrolled in the study between 06/22/2021 and 06/07/2024.
Participants were recruited from 06/22/2021 through 06/07/2024 at one center in Malawi.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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).. |
| FG001 | Low-risk Patients | Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | Low-risk Patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | All participants started the study. | Posted | Count of Participants | Participants | From the start of rituximab-based therapy to 12 weeks. (Up to 13 weeks) |
|
Up to 12 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Matthew S Painschab | UNC Lineberger Comprehensive Cancer Center | 919-966-4431 | matthew_painschab@med.unc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 20, 2022 | Jul 31, 2025 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| C537372 | Multi-centric Castleman's Disease |
| C537834 | Macular dystrophy, corneal type 1 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D005047 | Etoposide |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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 |
|
|
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. |
| 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. | 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). | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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. | Baseline, Day 15 and End of treatment (approximately 6 weeks) |
Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Low-risk Patients | Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone. |
|
|
| Secondary | 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. | Not Posted | Baseline - until 21 days | Participants |
| Secondary | 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. | Not Posted | 90 days, 1 year, and 2 years | Participants |
| Secondary | 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. | Not Posted | 90 days, 1 year, and 2 years | Participants |
| Secondary | 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). | Not Posted | At the end of the treatment, 12 weeks after start of the treatment | Participants |
| Secondary | 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. | Not Posted | At the end of the treatment, 12 weeks after start of the treatment | Participants |
| Secondary | 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. | Not Posted | At the end of the treatment, 12 weeks after start of the treatment | Participants |
| Secondary | 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). | Not Posted | First day of the treatment through 12 weeks (Up to 13 weeks) | Participants |
| Secondary | 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. | Not Posted | Up to 2 years | Participants |
| Secondary | 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. | Not Posted | Baseline, week3, end of the treatment, 12 weeks, 6 months after the treatment, 24 months after the treatment, time of relapse. | Participants |
| Secondary | 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. | Not Posted | Baseline, Day 15 and End of treatment (approximately 6 weeks) | Participants |
| Secondary | 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. | Not Posted | Baseline, Day 15 and End of treatment (approximately 6 weeks) | Participants |
| Secondary | 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. | Not Posted | Baseline, Day 15 and End of treatment (approximately 6 weeks) | Participants |
| Secondary | 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. | Not Posted | Baseline, Day 15 and End of treatment (approximately 6 weeks) | Participants |
| 1 |
| 9 |
| 1 |
| 9 |
| 9 |
| 9 |
| EG001 | Low-risk Patients | Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone. | 0 | 6 | 1 | 6 | 6 | 6 |
| neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypoalbuminemia | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alkaline Phosphatase Increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE (4.0) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Laryngeal Inflammation | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Neuralgia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Peripheral Sensory Neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |