Short-Course EPOCH - Rituximab in Untreated CD-20+ HIV-Associated Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 2
- 主要终点
- Median Progression Free Survival (PFS)
研究概览
简要总结
Background:
- Human immunodeficiency virus (HIV)-infected patients have a weakened immune system, and chemotherapy, which is used to treat lymphoma, probably causes further damage to the immune system.
- Limiting the amount of immune damage due to chemotherapy might decrease the number of infections and the risk of developing cancer in the future in HIV-infected patients with non-Hodgkin's lymphoma.
Objectives:
- To determine whether reducing the total amount of chemotherapy using a specific combination of drugs called EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will rid the body of lymphoma quickly while decreasing the risk of infections and future cancers.
- To determine whether the lymphoma will remain undetectable for at least one year if treatment is stopped one cycle after the patient enters remission.
Eligibility:
-Patients with non-Hodgkin's lymphoma and HIV infection 4 years of age and older who have not been treated previously with rituximab or cytotoxic chemotherapy.
Design:
- Patients receive EPOCH-R in 3-week treatment cycles for at least three and no more than six cycles.
- The lymphoma is evaluated using computed tomography (CT) and positron emission tomography (PET) scans at the end of treatment cycles 2 and 3. A bone marrow biopsy is repeated after cycle 2 if a biopsy was initially positive on screening for participation in the study.
- Anti-HIV therapy is stopped before chemotherapy begins and is restarted when EPOCH-R treatment ends.
- Patients are monitored for treatment response with blood tests and imaging scans at baseline, when treatment ends, 2 months after treatment ends and then every 3 to 6 months for a total of 24 months following chemotherapy.
详细描述
Background:
This is a study to investigate in a preliminary fashion the feasibility of short course chemotherapy to participants with HIV-associated non-Hodgkin's lymphoma (HIV-NHL).
This study will investigate if the paradigm for treatment can be successfully changed from a standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles.
Objective:
To assess with 90 percent probability that at least 50 percent of participants treated with short-course EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will be progression free at one year.
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
- •INCLUSION CRITERIA:
- •Aggressive B-lymphocyte antigen CD20 (CD20) positive Diffuse Large B-cell lymphoma confirmed by Laboratory of Pathology, National Cancer Institute (NCI). Note: Participants with aggressive B-cell lymphoma of the plasmablastic lymphoma sub-type who do not have surface CD20 expression, are also eligible.
- •Human immunodeficiency virus (HIV) + serology.
- •All stages (I-IV) of disease.
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-4
- •Non-Hodgkin's Lymphoma (NHL) previously untreated with cytotoxic chemotherapy; however, participants may be entered if they have had prior cyclophosphamide for an urgent problem at diagnosis (e.g., epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture
- •Age greater than or equal to 18 years
- •Laboratory tests (unless impairment due to respective organ involvement by tumor):
- •Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min
- •Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with direct fraction less than or equal to 0.3 mg/dl in participants for whom these abnormalities are felt to be due to protease inhibitor therapy
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x upper limit of normal (ULN) (AST and ALT less than or equal to 6x ULN for participants on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation)
- •Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3)
- •Platelet greater than or equal to 75,000/mm(3) (unless impairment due to Immune thrombocytopenic purpura (ITP)
- •Ability of participant to provide informed consent.
排除标准
- •Previous rituximab
- •Pregnancy or nursing.
- •- Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk.
- •Current clinical heart failure or symptomatic ischemic heart disease.
- •Serious underlying medical condition or infection other than HIV that would contraindicate subcutaneous (SC)-rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin (EPOCH-R).
- •Examples include, but are not limited to:
- •Severe Acquired immunodeficiency syndrome (AIDS)-related wasting
- •Sever intractable diarrhea
- •Active inadequately treated opportunistic infection of the central nervous system (CNS)
- •Primary CNS lymphoma
- •Primary CNS lymphoma
研究组 & 干预措施
Arm 1-Combination Chemo and Biological Therapy
Combination chemo and biological therapy
干预措施: EPOCH (Drug)
Arm 1-Combination Chemo and Biological Therapy
Combination chemo and biological therapy
干预措施: Rituximab (Biological)
Arm 1-Combination Chemo and Biological Therapy
Combination chemo and biological therapy
干预措施: Filgrastim (Biological)
结局指标
主要结局
Median Progression Free Survival (PFS)
时间窗: The participants were followed for a median of 15.4 years.
PFS is the time interval from study entry to documented evidence of disease progression or death due to any cause. Progression is defined according to the Cheson response criteria. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s). Confidence intervals were made, and a Kaplan-Meier curve of progression free survival was constructed.
Progression Free Survival at 1 Year
时间窗: 1 year
PFS is the time interval from start of treatment to documented evidence of disease progression. Progression is defined according to the Cheson response criteria. Disease progression as indicated by imaging scans at one year following therapy. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s).
次要结局
- Median Duration of Complete Response/Complete Response Unconfirmed(The participants were followed for duration of complete response or complete response unconfirmed for a median of 15.4 years.)
- Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)(Participants were followed for up to 10.2 years to determine their response on interim PET scans.)
- 1 Year Overall Survival(1 year)
- Number of Participants With at Least One Hematologic Toxicity Event of Febrile Neutropenia(Date treatment consent signed to date off study, approximately 209 months and 17 days.)
- 1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)(1 year)
- Recovery of Human Immunodeficiency Virus (HIV) Viral Load(Either following or concurrently with combination chemo and biological therapy, approximately every 6 to 8 weeks after therapy was completed up to 16 months)
- Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity(Date treatment consent signed to date off study, approximately 209 months and 17 days.)
- Median Overall Survival(The participants were followed for survival for a median of 15.4 years.)
- Percentage of Participants With CR/CRu Lasting 1 Year(1 year)
- Percentage of Participants With Complete Response(The participants were followed for an average of 6 months to determine response to therapy.)
- Recovery of CD4 T Cells (CD4) Counts(From the end of chemotherapy every 3 months for the first 2 years)
- Number of Cycles of Hematologic Toxicity(Up to 112 cycles (each cycle is 21 days + 7 days window))
- Overall Response(The participants were followed for an average of 6 months to determine response to therapy.)
研究者
Christopher Melani, MD
Principal Investigator
National Cancer Institute (NCI)