A Combination of Lenalidomide and Rituximab as Front Line Therapy for the Treatment of Elderly Frail Patients Evaluated in CGA With Diffuse Large B-cells Non-Hodgkin Lymphoma. A Phase II Study of the Fondazione Italiana Linfomi (FIL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 18
- 主要终点
- ORR
研究概览
简要总结
A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma.
详细描述
This is a prospective, multicenter, single arm, phase II trial in elderly patients (≥ 70 years) affected by DLBCL defined as frail according to CGA and previously untreated.
The primary endpoint is to evaluate the efficacy of the R2 (Revlimid+Rituximab) combination in first line DLBCL patients not candidate for the standard R-CHOP (or R-CHOP like) treatments due to the frail status.
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
- •Age ≥ 70 years
- •Previously untreated
- •CGA assessment performed before starting treatment
- •FRAIL patients defined as follows
- •Age > 80 years (with UNFIT profile):
- •ADL ≥ 5 residual functions and/or IADL ≥ 6 residual functions and/or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2
- •Age < 80 (ONLY one of the following criteria):
- •ADL ≤ 4 residual functions IADL ≤ 5 residual functions CIRS: 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2
- •Ann Arbor Stage I - IV (Appendix F)
- •At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
- •ECOG performance status of 0- 3 (Appendix E)
- •No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
- •Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:
- •Hemoglobin > 10 g/dL
- •WBC > 2500/mmc with PMN > 1000/ mmc
- •Platelets count ≥ 75000/mmc
- •Creatinine clearance ≥ 10 mL/min
- •Ability and willingness to comply with the study protocol procedure
- •Life expectancy > 6 months
- •Patients must give written informed consent.
- •Male subjects must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
排除标准
- •Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
- •Previous exposure to cytotoxic agents
- •Suspect or clinical evidence of CNS involvement by lymphoma
- •Contraindication to the use of Rituximab or of Lenalidomide
- •HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided.
- •HIV positivity
- •Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
- •Any history of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
- •AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL
- •Creatinine clearance < 10 mL/min
- •Evidence of any severe active acute or chronic infection
- •Severe cardiac dysfunction (NYHA grade III-IV)
- •Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
- •Absence of caregivers in non-autonomous patients
研究组 & 干预措施
1 arm for all patient: Ritux-Dexame-Lena
Rituximab-Dexamethasone-Lenalidomide
干预措施: Rituximab-Dexamethasone-Lenalidomide (Drug)
结局指标
主要结局
ORR
时间窗: 48 months
Overall response rate (ORR) is defined as the proportion of patients with complete and partial response respectively according to Cheson 2014 (Appendix K). The ORR rate will be evaluated both on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders. Response of R2 will be calculated for the EP according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014; patients will be categorized into Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Non Responders (NR).
Safety: clinical relevant toxicity
时间窗: 48 months
Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.
次要结局
- CR(48 months)
- OS(54 months)
- PFS(54 months)
- EFS(54 months)
- Quality of life(54 months)