Comparing the Efficacy and Safety of Reduced-dose Chemotherapy Followed by Blinatumomab Versus hyperCVAD as Induction Therapy for Newly Diagnosed Ph-negative B-ALL: a Multicenter, Radomized, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Composite complete remission rate
研究概览
简要总结
In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.
详细描述
Blinatumomab, a CD3/CD19 bisespecific T-cell conjugative antibody, has shown high efficacy in phase I/II studies of relapsed/refractory B-lymphoblastic leukemia (B-ALL), particularly in the context of low tumor burden.Meanwhile, Blinatumomab also plays an important role in rapid and efficient clearance of MRD in patients. Therefore, its use in combination with less intensive chemotherapy for initial induction therapy in newly diagnosed patients may result in favorable response rates, greater depth of remission, and lower treatment-related toxic effects.
In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.
The regimen of consolidation therapy is recommended as multidrug combination chemotherapy (including high-dose Methotrexate or Cytarabine combined with Asparaginase) or alternating with Blinatumomab (28 ug/d×28d). If Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is not performed, consolidation therapy needs at least 4 courses before 2 years maintenance therapy.
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
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 15-65
- •Ph-(BCR-ABL1 negative)B-ALL was diagnosed according to WHO diagnostic criteria
- •Newly diagnosed patients without prior induction therapy (except hydroxyurea and glucocorticoids ≦5 days
- •ECOG score 0-3
- •Liver function: total bilirubin ≦ 3 times the upper limit of normal; Alanine ·aminotransferase ≦ 3 times upper limit of normal motion; Aspartate aminotransferase ≦ 3 times upper limit of normal motion; (except considering leukemia infiltration)
- •Renal function: endogenous creatinine clearance ≧30ml/min
- •Patients must be able to understand and willing to participate in the study and must sign the informed consent form.
排除标准
- •Ph+ (BCR-ABL1 positive) ALL
- •T cells ALL
- •Mature B-cell leukemia/lymphoma, B-cell lymphoma, with extramedullary disease
- •Acute mixed-cell leukemia
- •Central nervous system leukemia
- •HIV infection
- •HBV-DNA or HCV-RNA positive
- •Patients with grade 2 or higher heart failure and other patients deemed inappropriate for inclusion by the investigator
- •Pregnant or breastfeeding patients
- •The study patient was refused enrollment
研究组 & 干预措施
Reduced-dose Chemotherapy Followed by Blinatumomab
Reduced-dose Chemotherapy(including 1 dose of Idarubicin 8 mg/m2, 1 dose of Vincristine 1.4 mg/m2[max 2mg], and 7 days of Dexamethasone 9 mg/m2/d) followed by 2 weeks of Blinatumomab (9 ug/d d8-14, 28 ug/d d15-21) immediately. If not achieved CR/CRi, Blinatumomab 28 ug for another 14 days should be continued.
干预措施: Blinatumomab Injection [Blincyto] (Drug)
hyperCVAD
CTX 300mg/m2 q12h D1-3 VCR 1.4mg/m2 (max 2mg) D4,D11 DNR 50mg/m2, D4 DEX 40mg/d D1-4, D11-14
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Composite complete remission rate
时间窗: Induction therapy phase: The time of bone marrow evaluation is day 28±7.
CR/CRi
次要结局
- Treatment-related AE(Induction therapy phase)
- Progression-free survival（PFS）(1 year after study completion)
- The negative rate of minimal residual lesion (MRD)(Induction therapy phase: The time of bone marrow evaluation is day 28 ±7.)
- Quality of survival of patients in the induction therapy phase(Induction therapy phase)
- Overall survival (OS)(1 year after study completion)
研究者
Chen Suning
Physician
The First Affiliated Hospital of Soochow University