A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 15
- 主要终点
- complete response rate (CRR)
研究概览
简要总结
This study will help researchers understand how effective the combination of venetoclax and rituximab is in treating MZL in people who have not received a previous treatment for their cancer.
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
- •Age greater than or equal to 18 years
- •Histologically confirmed Marginal Zone Lymphoma
- •Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm or spleen >13 cm.
- •°Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or colonoscopy with biopsy
- •Patients with gastric MALT lymphoma must be h. pylori negative
- •°Patients who are h. pylori positive are allowed if they have failed a trial of h.pylori eradication
- •Patients with gastric MALT lymphoma who are h. pylori negative or who have relapsed/refractory disease after h. pylori eradication must be ineligible for, have refused or failed gastric radiation therapy
- •ECOG performance status ≤ 1
- •Life expectancy of greater than 2 years
- •Patients must have normal organ function as defined below:
- •Platelet count ≥ 50,000 cells/mm^3
- •Hemoglobin ≥ 8.0 g/dL
- •Absolute neutrophil count ≥ 1000 cells/mcL. If there is documented bone marrow involvement, ANC must be >/= 500 cells/mcL
- •Total bilirubin < 1.5 x upper normal institutional limits. In patients with Gilbert's disease or documented liver involvement, total bilirubin up to 3x ULN will be allowed
- •AST(SGOT)/ALT(SGPT) <3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL
- •AST(SGOT)/ALT(SGPT) <3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL
- •°OR Creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements).
- •Ability to understand and the willingness to sign a written informed consent document.
- •Able to swallow pills
- •HIV-positive patients on combination antiretroviral therapy are eligible if their HIV is under adequate control with an antiretroviral regimen that has been stable for > 4 weeks, as long as the CD4 count is >
- •Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- •Patients with Hepatitis B surface antibody serum positivity due to prior immunization, as well as those with Hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible.
排除标准
- •Patients who have had prior systemic therapy, including rituximab
- •Patients who have had prior radiation therapy, with the following exception:
- •°Palliative radiotherapy RT is allowed but must be completed at least 1 week prior to treatment on this study, and prior baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT
- •Prior treatment with ibrutinib or other BTK inhibitor
- •Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded unless they are deemed to be unfit for radiation therapy with curative intent.
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •°Patients with Hep B core ab positivity are allowed provided Hep B PCR is undetectable
- •Lactating or pregnant women
- •Participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab
- •Patients who received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.
- •Patients who received moderate or strong CYP3A inducers (such as rifampin, carbamazepine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax.
研究组 & 干预措施
Rituximab and Venetoclax
Patients will be treated with an Induction phase of rituximab 375 mg/m2 weekly for 4 weeks. Patients will undergo restaging imaging after the last of 4 weekly rituximab doses and before beginning venetoclax. Based on post-rituximab restaging studies, patients will be risk-stratified for risk of Tumor Lysis Syndrome (TLS) and treated in the appropriate setting with TLS prophylaxis per institutional TLS guide lines starting at week 5. Oral venetoclax will follow a ramp-up dosing schedule and will be taken daily after 4 weeks of rituximab therapy. Following the 4-week ramped-up phase of venetoclax, patients will begin their target dose of venetoclax and continue for a maximum of 24 months. In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months. Venetoclax may be continued after this period if patient has not achieved a complete remission
干预措施: Rituximab (Drug)
Rituximab and Venetoclax
Patients will be treated with an Induction phase of rituximab 375 mg/m2 weekly for 4 weeks. Patients will undergo restaging imaging after the last of 4 weekly rituximab doses and before beginning venetoclax. Based on post-rituximab restaging studies, patients will be risk-stratified for risk of Tumor Lysis Syndrome (TLS) and treated in the appropriate setting with TLS prophylaxis per institutional TLS guide lines starting at week 5. Oral venetoclax will follow a ramp-up dosing schedule and will be taken daily after 4 weeks of rituximab therapy. Following the 4-week ramped-up phase of venetoclax, patients will begin their target dose of venetoclax and continue for a maximum of 24 months. In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months. Venetoclax may be continued after this period if patient has not achieved a complete remission
干预措施: Venetoclax (Drug)
结局指标
主要结局
complete response rate (CRR)
时间窗: 2 years
Will be evaluated in this study using the RECIL criteria.
次要结局
- overall response rates (ORR)(2 years)