An Open-label, Randomized, Phase 2 Study of R-CHOP Plus Enzastaurin Versus R-CHOP in the First-Line Treatment of Patients With Intermediate and High-Risk Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) Time
研究概览
简要总结
To compare R-CHOP plus enzastaurin versus R-CHOP for progression-free survival (PFS) time measured in participants with intermediate and/or high risk for diffuse large B-cell lymphoma (DLBCL) receiving first-line treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must:
- •Have a histologically confirmed diagnosis of DLBCL based on the World Health Organization classification (Harris et al. 1999) at the time of original diagnosis. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the participant is entered. Participants with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be eligible for enrollment.
- •Have received no prior chemotherapy.
- •Have an International Prognostic Index (IPI) score ≥2 at time of original diagnosis.
- •Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale.
- •Have adequate organ function as follows:
- •Hepatic: total bilirubin ≤1.5 times the upper limit of normal (x ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 x ULN, (≤5 x ULN, if liver involvement).
- •Renal: serum creatinine ≤1.5 x ULN.
- •Adequate bone marrow reserve: platelets ≥75 x 10^9 per Liter (L), absolute neutrophil count (ANC) ≥1.0 x 10^9 per L, unless there is bone marrow involvement.
排除标准
- •Participants must not:
- •Have received treatment within the last 30 days with a drug (not including enzastaurin) that has not received regulatory approval for any indication at the time of study entry.
- •Are receiving concurrent administration of any other systemic anticancer therapy.
- •Are pregnant or breastfeeding.
- •Are unable to swallow tablets.
- •Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin at least 14 days prior to study enrollment.
研究组 & 干预措施
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: enzastaurin (Drug)
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: rituximab (Drug)
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: cyclophosphamide (Drug)
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: doxorubicin (Drug)
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: vincristine (Drug)
R-CHOP and Enzastaurin
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: prednisone (Drug)
R-CHOP
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: rituximab (Drug)
R-CHOP
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: cyclophosphamide (Drug)
R-CHOP
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: doxorubicin (Drug)
R-CHOP
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: vincristine (Drug)
R-CHOP
R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
干预措施: prednisone (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Time
时间窗: Randomization to measured PD or death from any cause (up to 55 months)
PFS time is the elapsed time from the date of randomization to the first date of objectively-determined PD or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (other than enzastaurin maintenance therapy) prior to objectively determined disease progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of subsequent therapy.
次要结局
- Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate)(Baseline through long-term follow-up (up to 2 years post last dose))
- Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan)(Cycle 6 (21 days/cycle))
- Event-Free Survival (EFS)(Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months))
- Percentage of Participants Alive Progression-Free at Year 2 (2-Year PFS Rate)(Randomization to measured PD (up to Year 2))
- Percentage of Participants With a PET-Negative Scan (PET-Negative Rate)(Cycle 6 (21 days/cycle))
- Overall Survival (OS)(Baseline to death from any cause (up to 55 months))
- Duration of Complete Response (CR or CRu)(Time of response to PD (up to 55 months))
- Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)(First dose through 30 days post study treatment discontinuation (up to 56 months))
- PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS(Randomization to measured PD or death from any cause (up to 55 months)])