HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- PFS Evaluation
研究概览
简要总结
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
详细描述
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
All patients with untreated or R/R (not previously treated with Bendamustine) iNHL (Follicular Lymphoma (Grade 1-3a2), Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma) are candidates for this trial. Patients requiring treatment per treating physician's discretion are eligible for the trial.
Patients who recently started on and received two cycles of Bendamustine at 90 mg/m2 dose with Ritxumab 375 mg/m2 are also eligible for this trial. For these patients, C2D1 BR should be no more than 14 days prior to the time of study enrollment (i.e. enrollment no later than C2D14). Patients who have received two cycles of 90mg/m2 Bendamustine dose with Rituximab 375 mg/m2 can enter the study and initiate cycle 3 once pre-screening and screening procedures have been completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have pathologically confirmed:
- •indolent Non-Hodgkin Lymphoma, consistent with one of the below diagnoses:
- •Follicular Lymphoma (Grade 1-3a)
- •Marginal Zone Lymphoma
- •Lymphoplasmacytic Lymphoma
- •Patient may be treatment naïve or relapsed/refractory without having received prior Bendamustine or patients recently started on Bendamustine 90 mg/m2 with Rituximab 375 mg/m2 are eligible if C2D1 BR is no more than 14 days prior to enrollment and they otherwise meet eligibility criteria
- •Age > 18 years
- •ECOG performance status 0-2
- •Patients must have normal organ and marrow function as defined below:
- •Absolute Neutrophil Count >1000mm3 and Hemoglobin >8 g/dL (unless due to bone marrow involvement by lymphoma)
- •Total bilirubin > 1.5x upper limit of normal (patients with Gilbert's syndrome can have total bilirubin up to 3x upper normal limit)
- •Aspartate aminotransferase/ alanine aminotransferase (serum glutamic-oxaloacetic transaminase/ serum glutamic-pyruvic transaminase) < 5 times institutional normal limits
- •Creatinine clearance > 30 Ml/min
排除标准
- •Radiation or systemic treatment for lymphoma within the past 28 days prior to cycle 1 day 1 of BR.
- •Patients with pathologically confirmed transformed lymphoma, including diffuse large B cell lymphoma or other high grade lymphomas
- •Patients on active treatment for second malignancy with the exception of endocrine therapy for non-metastatic breast cancer, hormone therapy for prostate cancer, or local treatment for non-melanoma skin cancer.
- •Pregnant or breast-feeding. Refer to section 5.4 for further detail.
- •Failure to identify a dominant clonal sequence with ClonoSEQ from pre-treatment specimen or inadequate tissue for testing
研究组 & 干预措施
Single Arm
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of Measurable Residual Disease (MRD) adapted duration of BR for untreated or R/R iNHL (indolent non-hodgkin lymphoma). All patients will receive Bendamustine 90 mg/m2 IV on Days 1-2 and Rituximab 375 mg/m2 IV(BR) on Day 1 of each cycle. Each cycle will last 28 days. On day 1 of each cycle, patients will receive Rituximab before Bendamustine, and CBC (complete blood count), CMP (comprehensive metabolic panel) will be obtained to capture any hematologic toxicities as well as clonoSEQ testing to determine MRD status. After completing Cycle 3, imaging results (with confirmatory biopsy if applicable) and the clonoSEQ MRD testing results obtained from ctDNA (blood collection) will determine whether patients will receive Cycles 5 and 6 of Bendamustine and Rituximab (BR).
干预措施: Bendamustine (Drug)
Single Arm
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of Measurable Residual Disease (MRD) adapted duration of BR for untreated or R/R iNHL (indolent non-hodgkin lymphoma). All patients will receive Bendamustine 90 mg/m2 IV on Days 1-2 and Rituximab 375 mg/m2 IV(BR) on Day 1 of each cycle. Each cycle will last 28 days. On day 1 of each cycle, patients will receive Rituximab before Bendamustine, and CBC (complete blood count), CMP (comprehensive metabolic panel) will be obtained to capture any hematologic toxicities as well as clonoSEQ testing to determine MRD status. After completing Cycle 3, imaging results (with confirmatory biopsy if applicable) and the clonoSEQ MRD testing results obtained from ctDNA (blood collection) will determine whether patients will receive Cycles 5 and 6 of Bendamustine and Rituximab (BR).
干预措施: Rituximab (Drug)
结局指标
主要结局
PFS Evaluation
时间窗: 2 years
To evaluate the 2-year progression free survival (PFS) for patients treated with Bendamustine and Rituximab (BR) with measurable residual disease directed (MRD) duration of therapy.
Statistical PFS
时间窗: 2 years
The proportion (p) of patients who are progression-free and are alive at 2 years from the initiation of treatment using Lugano Criteria.
次要结局
- Measurable Residual Disease Negativity(2 years)
- Overall Survival Assessment(2 years)
- Secondary Outcome Measure(2 years)
- Measurable Residual Disease Evaluation(2 years)
- Adverse Event assessment(2 years)
- Rate of 3+ adverse events(2 years)