Single Cycle of Blinatumomab Followed by High-dose Chemotherapy in the Induction Therapy for Ph-negative Acute Lymphoblastic Leukemia in Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Complete Molecular Response
研究概览
简要总结
This is a phase II interventional trial to evaluate the efficacy of blinatumomab followed by high-dose chemotherapy in the first-line treatment for Ph-negative acute lymphoblastic leukemia (ALL) in adults. The aim is to increase the number of complete molecular responses after first two cycles of therapy. Early molecular response is considered to be the most powerful prognostic factor in ALL. Thus, a higher proportion of early molecular responses should translate into improved survival and fewer indications for allogeneic stem cell transplants
详细描述
Primary Objective:
To evaluate the percentage of complete molecular responses after two cycles of induction therapy composed of a single cycle of blinatumomab followed by chemotherapy. Molecular response id monitored by a patient-specific Ig/TCR rearrangements in an assay with the sensitivity of at least 10e-04.
Outline:
Run-in phase: dexamethasone 10 mg/m2 PO (day 1-7), cyclophosphamide IV 200 mg/m2 (day 3-5), vincristine 2 mg IV (day 6), daunorubicin 45 mg/m2 IV (day 6-7), G-CSF until recovery, methotrexate 15 mg IT.
Day 11: Screening to the study. Induction I: blinatumomab 9 µg/day IV continuously (day 12-19), dose step to 28 µg/day (day 19-40). Induction II: dexamethasone 10 mg/m2 PO (day 50-54), vindesine 3 mg/m2 IV (day 50), methotrexate 1.5 g/m2 IV (day 50), etoposide 250 mg/m2 IV (day 53-54), cytarabine 2x 2 g/m2 IV (day 54), G-CSF until recovery, methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 60).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years;
- •Lymphoblasts positive for CD19;
- •Eligible to intensive chemotherapy, due to general health status;
- •With newly diagnosed B-precursor-ALL;
- •Without BCR-ABL fusion by FISH analysis and/or RT-PCR;
- •Blasts expressing the CD19 antigen by flow cytometry;
- •Previously untreated;
- •ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2;
- •Diagnostic sample of bone marrow (or peripheral blood with >50% of blasts) available for central MRD assessment
- •Written informed consent obtained prior to any screening procedures.
排除标准
- •History of malignancy other than ALL within 5 years prior to start of protocol-required therapy, except for:
- •Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician;
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
- •Adequately treated cervical carcinoma in situ without evidence of disease;
- •Adequately treated breast ductal carcinoma in situ without evidence of disease;
- •Prostatic intraepithelial neoplasia without evidence of prostate cancer.
- •History or presence of central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis;
- •Persisting ALL in the CNS at the end of run-in period; patients with initial cerebrospinal fluid (CSF) infiltration arriving into CSF negativity after up to 4 intrathecal applications of chemotherapy within the first 10 days of therapy are allowed for the study;
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement;
- •Active known hepatitis B virus (HBV) or hepatitis C virus (HCV) or positive HIV serology;
- •Hypersensitivity to any active substance contained in blinatumomab, including polysorbate 80;
- •Vaccination with a live virus vaccine within 4 weeks prior to the study enrolment;
- •Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug;
- •Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a double barrier method of contraception, one of which includes a condom, during the study;
- •Any of concurrent severe and/or uncontrolled medical condition, which could, in the opinion of the investigator, compromise participation in the study;
- •Concurrent participation in another clinical study with an investigational medical product.
研究组 & 干预措施
Blinatumomab followed by high-dose chemotherapy
Single cycle of blinatumomab followed by high-dose chemotherapy in the induction therapy for Ph-negative acute lymphoblastic leukemia in adults
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Complete Molecular Response
时间窗: At week 11 (acceptable window +2wks); after completion of two induction courses (1st Induction Course is 28 days) and before starting of the 1st Consolidation cycle at week 13
Percentage of complete molecular responses after two cycles of induction therapy composed of a single cycle of blinatumomab followed by chemotherapy
次要结局
- Progression Free Survival (PFS)(Time from the day of CR/CRi documentation until the date of relapse, or death from any cause whichever came first, assessed up to 24 months)
- AlloSCT(Week 18 ( after the completion of the 1st Consolidation cycle which is 21 days))
- Infectious complications during induction chemotherapy(At week 11; after completion of two induction courses (1st Induction Course is 28 days))
- Minimal Residual Disease (MRD) response(End of blinatumomab infusion (End of the 1st Induction course which is 28 days); Day 40 of the study)
- Incidence and severity of blinatumomab-related adverse events(At week 11; after completion of two induction courses (1st Induction Course is 28 days))
- Overall Survival (OS)(Time between the start of leukemia-specific therapy (Day 1) until date of death of any cause, assessed up to 24 months)