Phase I/II Trial of Decitabine + R-CHOP in Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- maximum tolerated dose
研究概览
简要总结
This is a Phase I/II Trial of Decitabine + R-CHOP in Diffuse Large B-Cell Lymphoma
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
- 15 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically confirmed DLBCL, CD20 positive.
- •must have at least one site of measurable disease, 1.5 cm in diameter or greater.
- •has not had any previous treatment.
- •International Prognostic Index >
- •Able to adhere to the study visit schedule and other protocol requirements.
- •must have laboratory test results within these ranges: Absolute neutrophil count ≥1500/mm3 Platelet count≥75,000/mm3 Serum creatinine≤1.5×upper limit of normal (ULN) Total bilirubin≤1.5×ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
- •AST (SGOT) and ALT (SGPT) ≤2×ULN
- •Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- •Women of childbearing potential must have a negative serum pregnancy test prior to Decitabine treatment.
- •Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with Decitabine. The effects of Decitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Age 15 to 75 years.
- •Ability to understand and the willingness to sign a written informed consent document.
- •ECOG performance status of 0-2
排除标准
- •Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Use of any other experimental drug or therapy within 28 days of baseline.
- •Concurrent use of other anti-cancer agents or treatments.
- •Known positive for HIV. If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA, DNA positive patients cannot be enrolled.
- •Known central nervous system involvement by lymphoma.
- •Known or suspected hypersensitivity to Decitabine or mannitol.
- •Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
研究组 & 干预措施
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Rituximab (Drug)
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Cyclophosphamide (Drug)
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Doxorubicin (Drug)
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Vincristine (Drug)
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Prednisone (Drug)
Decitabine plus R-CHOP
Rituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11;
Decitabine will be administered intravenously at dose levels as follow in Phase 1:
Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose.
In phase 2, Decitabine will be administered intravenously at MTD.
干预措施: Decitabine (Drug)
结局指标
主要结局
maximum tolerated dose
时间窗: day1 to 21
The primary endpoint for the phase I portion of the study is to determine the maximum tolerated dose of Decitabine when given in combination with a standard dose (q21 day) regimen of R-CHOP in patients with DLBCL.
complete response rate
时间窗: 21 days after 6 cycles of treatment (each cycle is 21 days)
The primary endpoint for the phase II portion of the study will be complete response rate.
次要结局
- Overall response rate(21 days after 6 cycles of treatment (each cycle is 21 days))
- Event-free survival(2 years)
- Overall survival(2 years)
- Progression-free survival(2 years)
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0(Up to 30 days after completion of study treatment)