Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma
A Phase I and Feasibility Study of Everolimus (RAD001) Plus R-CHOP for New Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer cells in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Giving everolimus together with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and the best dose of everolimus when given together with rituximab and combination chemotherapy in treating patients with newly diagnosed untreated diffuse large B-cell lymphoma.
研究概览
地位
条件
详细说明
OBJECTIVES:
Primary
- To establish the maximum-tolerated dose (MTD) of everolimus in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone) chemotherapy.
- To assess the feasibility of everolimus in combination with standard R-CHOP chemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma.
Secondary
- To describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To further describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To assess the rate of event-free survival (EFS) at 12 months for diffuse large B-cell lymphoma patients treated with everolimus in combination with R-CHOP chemotherapy.
- To evaluate overall response rate, complete response rate, duration of response, EFS, overall survival, and progression-free survival for patients treated with everolimus in combination with R-CHOP chemotherapy.
Tertiary
- To profile gene expression using immunohistochemistry and categorize patients as germinal-center B-cell-like (GBC) vs activated B-cell-like (ABC) vs unclassified lymphoma subtype. (exploratory)
- To determine whether previously identified predictive markers in large cell lymphoma remain valid with the addition of everolimus to R-CHOP chemotherapy. (exploratory)
OUTLINE: This is a multicenter, dose-escalation study of everolimus followed by a feasability expanded-cohort study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-10 or 1-14; rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV over 15-60 minutes, and vincristine sulfate IV on day 1; and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Tumor biopsies are collected for laboratory studies and patients may undergo blood and needle biopsy sample collection for correlative studies.
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Minnesota
-
Rochester、Minnesota、美国、55905
- Mayo Clinic Cancer Center
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
- Untreated, histological diagnosis of CD20-positive diffuse large B-cell lymphoma
- Stage II-IV (Ann Arbor Staging)
Measurable or assessable disease defined as at least one of the following:
- A lymph node or tumor mass that is ≥ 2.0 cm in at least one dimension by CT portion of PET/CT scan, CT scan, or MRI
- Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease
- Diagnostic tissue slides and paraffin-embedded block must be available
- No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count (ANC) ≥ 1,500/mm³
- Peripheral platelet count ≥ 100,000/mm³
- Hemoglobin (HgB) > 9.0 g/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- For total bilirubin > 1.5 times ULN, the direct bilirubin must be normal
- Alkaline phosphatase ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
- AST ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
- Creatinine ≤ ULN
- Negative serum or urine pregnancy test
- Not pregnant or nursing
- Men or women of childbearing potential must be willing to employ adequate contraception throughout the study and for12 months after the last dose of study drug
- Willing to return to the National Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
- Willing to provide archival tissue from the primary diagnosis (original lymphoma lymph node tissue biopsy)
- Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
- Diabetic patients who are taking insulin or oral anti-diabetic therapy must have HbA1c ≤ 8%, or a fasting serum glucose ≤ 110% ULN
- HIV-positive patients must have CD4 count ≥ 400/mm³
- No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- No immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive with a CD4 count of < 400/mm³
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Severely impaired lung function
Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN
- Optimal glycemic control should be achieved before starting trial therapy
- Psychiatric illness/social situations that would limit compliance with study requirements
- Liver disease such as cirrhosis or severe hepatic impairment
- Chronic active hepatitis
- Chronic persistent hepatitis or history of hepatitis B or C
No other active malignancy except non-melanotic skin cancer or carcinoma in situ of the cervix
- If there is a history of prior malignancy, patients must not be receiving other specific treatment (other than hormonal therapy) for their cancer
No positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests meeting the following criteria:
- Hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core (anti-HBc) or hepatitis C antibody
- All patients must be screened prior to registration
- Patients who have evidence of chronic or acute infection with either hepatitis B or C may not be treated on this protocol
PRIOR CONCURRENT THERAPY:
- Not receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
No planned immunization with attenuated live vaccines ≤ 7 days prior to registration or during study period
- Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus
- Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines
- Not currently on enzyme-inducing anti-convulsants or other strong inducers of CYP3A4 (efavirenz, nevirapine, barbiturates, carbamazepine, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, pioglitazone, or St. John wort) or strong inhibitors of CYP3A4 (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, saquinavir, or telithromycin)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:everolimus and RCHOP
Patients registered to the study will receive an assigned dose of everolimus by mouth and RCHOP for a maximum of six cycles.
Each cycle is a total of 21 days.
RCHOP consists of 375 mg/m2 IV rituximab, 750 mg/m2 IV cyclophosphamide, 50 mg/m2 IV doxorubicin, 1.4 mg/m2 IV vincristine and 100 mg/m2 by mouth QD prednisone.
The study includes a Phase I component to determine the maximum tolerated dose of everolimus and the second component determines the feasibility of therapy administered to lymphoma patients.
|
四、
四、
PO
IV
PO
PO
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
MTD of everolimus in combination with R-CHOP
大体时间:Up to 15 months post registration to Phase I portion of the study
|
Up to 15 months post registration to Phase I portion of the study
|
Adverse events profile
大体时间:Up to 15 months post registration to Phase I portion of the study
|
Up to 15 months post registration to Phase I portion of the study
|
Toxicity profile
大体时间:Up to 15 months post registration to Phase I portion of the study
|
Up to 15 months post registration to Phase I portion of the study
|
Proportion of patients who have a significant toxicity
大体时间:Up to 2.5 years post registration to Feasibility portion of the study
|
Up to 2.5 years post registration to Feasibility portion of the study
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Rate of EFS
大体时间:Up to 5 years post treatment of the feasibility portion of the study
|
Up to 5 years post treatment of the feasibility portion of the study
|
Overall response rate, CR rate, overall survival, PFS, and duration of response
大体时间:Up to 5 years post treatment of the feasibility portion of the study
|
Up to 5 years post treatment of the feasibility portion of the study
|
合作者和调查者
调查人员
- 学习椅:Patrick Johnston, MD, PhD、Mayo Clinic
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NCCTG-N1085
- CDR0000698584 (注册表标识符:PDQ (Physician Data Query))
- NCI-2011-02643 (注册表标识符:CTRP (Clinical Trials Reporting System))
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
环磷酰胺的临床试验
-
Tianjin Medical University Cancer Institute and...CSPC Ouyi Pharmaceutical Co., Ltd.尚未招聘