A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 113
- 试验地点
- 126
- 主要终点
- Progression Free Survival
研究概览
简要总结
The purpose of this study is to find out what effects (good and/or bad) treatment with chemotherapy and stem cell transplant compared with chemotherapy alone will have on primary CNS B-cell lymphoma. Currently the best treatment for patients with primary CNS B-cell lymphoma is not known.
详细描述
Primary Objective:
To compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide
Secondary Objectives:
- To compare the two-year event-free survival (EFS) of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
- To compare the overall survival (OS) of patients treated with the consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
- To assess the toxicities associated with consolidation HDT/ASCT versus consolidation consisting of etoposide and cytarabine
- To determine diffusion MRI metrics (ADCmini, ADC25%, and ADCmean) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
- To determine brain FDG-PET metrics (tumor SUV and tumor versus background SUV) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
- To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101)
- To determine whether reduction in tumor SUV by > 25% on brain FDG-PET/CT after one cycle of induction therapy is associated with improved PFS and OS (CALGB 581101)
- To determine which IHC-based biomarkers are predictive of an adverse prognosis (CALGB 151113)
- To determine which IHC-based biomarkers are predictive of a favorable prognosis (CALGB 151113) for BCL6 (B-cell CLL/lymphoma 6), and STAT 6 (signal transducer and activator of transcription 6, interleukin-4 induced)
- To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113)
- To determine whether CSF proteome is a predictor of outcomes (prognostic marker) irrespective of treatment arm (CALGB 151113) for (IL-10 (interleukin 10) and C3 (complement component 3)
- To assess the neurocognitive function of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy (etoposide and cytarabine) as measured by serial administration of the International PCNSL Collaborative Group (IPCG) neurocognitive battery and evaluate the long-term survivorship differences between the two arms (CALGB 71105)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of Disease: Diagnosis of primary CNS diffuse large B-cell lymphoma confirmed by one of the following: brain biopsy or resection, cerebrospinal fluid and vitreous fluid.
- •Other Lymphomas: Patients must have no evidence or history of non-Hodgkin lymphoma (NHL) outside of CNS.
- •Previous Treatment: Patients must have no prior chemotherapy or radiation therapy for lymphoma.
- •Age- Patients must be between the ages of 18 and 75 years.
- •Karnofsky Performance Scale - Patients must measure Karnofsky Performance Scale ≥ 30 (≥ 50 for patients ages 60-70).
- •Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test 10-14 days prior to registration; in addition, women and men of childbearing potential must commit to use an effective form of contraception throughout their participation in this study; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
- •HIV - Patients must have negative HIV serology.
- •Hepatitis - Patients must have negative HCV serology (unless HBsAb positive patient has recently received HBV vaccine, in this case HBcAb should be negative). All patients must be screened for hepatitis B infection before starting treatment. Those patients who test positive for hepatitis B should be closely monitored for evidence of active HBV infection and hepatitis during and for several months after rituximab treatment. PCNSL patients with a history of hepatitis B infection should be treated with entecavir or lamivudine (physician discretion for choice of drug) as antiviral prophylaxis to prevent hepatitis B reactivation.
- •Organ Transplant or Immunosuppressant Therapy - Patient must have no history of organ transplantation or ongoing immunosuppressant therapy.
- •Required Initial Laboratory Values: ANC ≥ 1500/mcL, AST and ALT < 2 x upper limit of normal (ULN), total bilirubin ≤ 3 mg/dL, creatinine clearance ≥ 50 mL/min, platelet count ≥ 100,000/mcL
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.
干预措施: carmustine (Drug)
Arm I
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.
干预措施: thiotepa (Drug)
Arm I
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.
干预措施: stem cell transplant (Procedure)
Arm I
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.
干预措施: G-CSF (Drug)
Arm II
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.
干预措施: cytarabine (Drug)
Arm II
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.
干预措施: etoposide (Drug)
Arm II
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.
干预措施: G-CSF (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 2 years
The primary endpoint is to compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide. PFS time = time from Registration to earliest date of Progression or Death due to any cause, censoring non-progressed and alive patients at the date of last disease status evaluation. Response will be defined using the modified IPCG criteria. Progressive disease is defined as \> 25% increase in contrast-enhancing CNS (brain and spine if latter abnormal at baseline) disease, appearance of any new, measurable (\>/= 10mm) contrast-enhancing disease or recurrent or new ocular or CSF disease.
次要结局
- Event Free Survival(2 years)
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0(7 years)
- Overall Survival(2 years)