LCCC 1950 - Rituximab for Multicentric Castleman Disease in Malawi, A Single-Arm Phase II Safety/Efficacy Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of Participant With Non-hematologic Grade ≥3 Adverse Events (AEs)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%
- •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.
排除标准
- •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.
- •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 >
- •Pregnant or breastfeeding (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).
研究组 & 干预措施
Single Arm Rituximab
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.
干预措施: Rituximab (Drug)
Single Arm Rituximab
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.
干预措施: Etoposide (Drug)
结局指标
主要结局
Number of Participant With Non-hematologic Grade ≥3 Adverse Events (AEs)
时间窗: From the start of rituximab-based therapy to 12 weeks. (Up to 13 weeks)
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).
次要结局
- Clinical Response Rate(At the end of the treatment, 12 weeks after start of the treatment)
- Radiological Response Rate(At the end of the treatment, 12 weeks after start of the treatment)
- Additional Safety(First day of the treatment through 12 weeks (Up to 13 weeks))
- 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)
- Radiological Response Rate(At the end of the treatment, 12 weeks after start of the treatment)
- Additional Safety(First day of the treatment through 12 weeks (Up to 13 weeks))
- The Rate of Kaposi Sarcoma Exacerbation(Up to 2 years)
- Quality of Life- Patient-reported Outcomes Questionnaires(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(Baseline, Day 15 and End of treatment (approximately 6 weeks))
- Change in Platelet Count Measurement(Baseline, Day 15 and End of treatment (approximately 6 weeks))
- Change in C-reactive Protein Measurement(Baseline, Day 15 and End of treatment (approximately 6 weeks))
- Change in Kaposi Sarcoma Herpesvirus Viral Load Measurement(Baseline, Day 15 and End of treatment (approximately 6 weeks))