A Multicenter, Single-arm Study to Assess the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (Blast Successor Trial)
概览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Goethe University
- 入组人数
- 83
- 试验地点
- 22
- 主要终点
- MRD response after one cycle
概览
简要总结
This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in patients with MRD of B- precursor ALL in complete hematological remission including patients with relapse after SCT. The study aims to expand experience generated in previous trials in patients with MRD positive ALL with a focus on additional specific questions.
详细描述
Transfer of patients to alloHSCT after one cycle or after a subsequent cycle is considered as per protocol discontinuation and as premature treatment discontinuation.
In case of hematological or extramedullary relapse, the study treatment will be permanently discontinued.
There will be a safety follow-up visit at 30 days after end of the last infusion. There will be efficacy follow-up until 18 months after treatment start. In patients scheduled for SCT the 30-day safety-visit may be performed at the latest time point possible before initiation of subsequent treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with CD19 positive B-precursor ALL in complete hematological remission defined as less than 5% blasts in bone marrow after at least three intense chemotherapy blocks (e.g., GMALL induction I-II/consolidation I).
- •Presence of minimal residual disease (MRD) after an interval of at least 8 days from last systemic chemo-therapy
- •at a level of ≥10-4 - \<10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 documented after an interval of at least 2 weeks from last systemic chemotherapy OR
- •at levels below 10-4 documented after an interval of at least 2 weeks from last systemic chemotherapy:
- •Positive \<10-4, non quantifiable (MolNE1) OR
- •Positive \<10-4 (MolNE2) OR
- •Presence of minimal residual disease (MRD), non quantifiable (MolNE3).
- •For evaluation of MRD patients must have at least one molecular marker based on individual rearrangements of immunoglobulin, TCR-genes or other suitable genes evaluated by the reference laboratory of the trial
- •Bone marrow function as defined below:
- •ANC (Neutrophils) \>= 1,000/µL
排除标准
- •Ph/BCR-ABL positive ALL
- •Presence of circulating blasts or current extramedullary involvement by ALL
- •History or presence of clinically relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis)
- •Current detection of ALL blast cells in cerebro-spinal fluid
- •History of or active relevant autoimmune disease
- •Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
- •Radiotherapy within 4 weeks prior to study treatment
- •Live vaccination within 2 weeks before the start of study treatment
- •Autologous hematopoietic stem cell transplantation (SCT) within six weeks prior to study treatment
- •Allogeneic SCT within 12 weeks before the start of study treatment
研究组 & 干预措施
Blinatumomab
Patients will receive four cycles of treatment, unless criteria for treatment discontinuation apply. The duration of one cycle is 6 weeks, including a four week continuous intravenous infusion and a two week infusion free interval, which may be extended by a maximum of 7 days.
Patients entered with MRD level <10-4 (non quantifiable/MolNE1, quantifiable/MolNE2) or positive MRD, non quantifiable (MolNE3) will receive up to two cycles of Blinatumomab.
Transfer of patients to alloHSCT after one cycle or after subsequent cycles is considered as per protocol discontinuation and as premature treatment discontinuation In case of hematological or extramedullary relapse, the study treatment will be permanently discontinued.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
MRD response after one cycle
时间窗: after one cycle of treatment (up to 43 days)
Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT
次要结局
- Continuous complete remission(18 months following initiation of blinatumomab)
- Serious Adverse Event (SAE) incidence(continuously until End of Safety-Follow-Up (up to 26 weeks))
- treatment related mortality after subsequent SCT(after subsequent SCT (at day 100 and later))
- GvHD(until End of Safety-Follow-Up (up to 26 weeks))
- treatment related mortality(continuously until End of Follow-Up (up to 18 Months))
- Quality of Life(until End of Follow-Up (up to 18 Months))
- Overall survival(18 months following initiation of blinatumomab)
- MRD response after two cycles(after two cycles of treatment (up to 85 days))
- Biological evaluation of hematological and extramedullary relapse(In Case of Relapse, continuously until End of Follow-Up (up to 18 Months))
- Hematological relapse-free survival(18 months following initiation of blinatumomab)
- Relapse localisations(In Case of Relapse, continuously until End of Follow-Up (up to 18 Months))
- complete MRD response after two cycles(after two cycles of treatment (up to 85 days))
- duration of MRD response(18 months following initiation of blinatumomab)
- Time to MRD response(MRD determination after each cycle of treatment (up to 24 weeks))
研究者
Nicola Goekbuget
Principal Investigator
Goethe University