Evaluation of Efficacy and Safety of Obinutuzumab Preemptive Treatment at the Time of the Molecular Relapse After First Line Immunochemotherapy With Autologous Stem Cell (ML29157).
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- MRD negativity defined as a MRD level
研究概览
简要总结
The objective of the study is the evaluation of efficacy and safety of obinutuzumab preemptive treatment at the time of the molecular relapse after first line immunochemotherapy with autologous stem cell transplantation in mantle cell lymphoma patients.
详细描述
Patients with evidence of MCL molecular relapse defined as an increasing copy number in quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes according to BIOMED-2 methodology and protocols in peripheral blood or/and bone marrow without evidence of clinical relapse/progression after auto-HCT procedure with all inclusion and no exclusion clinical trial criteria will receive 4 weekly infusions of obinutuzumab (1000 mg, iv) on day 1, 8, 15, 22.Response assessment in bone marrow and/or peripheral blood and CT/MRI imaging will be performed 2 months after the obinutuzumab preemptive treatment. Patients with subsequent molecular remission in peripheral blood and/or bone marrow confirmed in RQ-PCR (with 10-4 level of sensitivity) assessment and no signs of relapse/progression according to the Lugano Classification will be further followed. From this moment, evaluation of response will be performed every 6 months with computed tomography/magnetic resonance (CT/MR) imaging and bone marrow aspiration to detect classical relapse/progression and/or to detect subsequent molecular relapse by quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes with the use of consensus JH probes and specific ASO primers. Patients will be monitored every 3 months (outpatient visits with peripheral blood samples for MRD assessment to detect molecular relapse by quantitative RQ-PCR of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes). Preemptive treatment can be administered in subsequent molecular relapses/progressions.
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
- •Patients with evidence of MCL molecular relapse in peripheral blood or/and bone marrow,
- •Diagnosis of mantle cell lymphoma confirmed by histopathology
- •Presence of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion gene as a molecular marker used for minimal residual disease (MRD) assessment,
- •Patients in CR/PR after first-line treatment with myeloablative consolidation and ASCT,
- •Patients without evidence of mantle cell lymphoma progression/relapse according to the Lugano Classification criteria (2014),
- •ECOG performance status ≤ 2,
- •Signed patient's informed consent form,
- •Survival prognosis > 6 months,
- •Women of childbearing potential must have a negative pregnancy test result prior to initiation of treatment with the study medication and must consent to undergo pregnancy tests during the treatment period.,
- •Women of child-bearing potential must consent either to sexual abstinence or to using effective contraception (that results in a failure rate of < 1% per year) while receiving the study medication and for 18 months after its discontinuation,
- •Men must consent either to using an acceptable contraception method (that results in a failure rate of < 1% per year) or continued sexual abstinence while receiving the study medication and for 6 months after its discontinuation.
排除标准
- •Central nervous system involvement,
- •Chemotherapy, radiation therapy or any other antineoplastic treatment (including steroids, monoclonal antibodies or medications at the stage of clinical studies, before receiving marketing authorisation) after ASCT and before administration of the study medication,
- •Major surgery within 28 days prior to the study treatment initiation,
- •Renal impairment (plasma creatinine concentration > 1.5 × upper limit of normal and/or creatinine clearance ≤ 40 ml/h),
- •Hepatic impairment (total bilirubin concentration > 1.5 × upper limit of normal, AST and ALT > 2.5 × upper limit of normal),
- •Hb< 9 g/dl, ANC < 1.5 G/l, platelets < 75 G/l,
- •International normalized ratio (INR) > 1.5,
- •Clinically significant heart disease, including uncontrolled arrhythmias, unstable coronary artery disease, serious congestive circulatory failure (NYHA III-IV), myocardial infarction within 6 months before enrolment,
- •Other comorbidities, not responding to treatment, including, but not limited to: hematopoietic system diseases, gastrointestinal system diseases, endocrine system diseases, respiratory system diseases, neurological diseases, cerebral diseases and mental diseases that could affect compliance with the protocol or interpretation of results,
- •Active infections (viral, bacterial, fungal),
- •Coexistence of another neoplasm or a history of neoplastic disease (except for adequately treated basal cell carcinoma or squamous cell skin carcinoma, in situ cervical cancer or other neoplasm if the patient is in complete remission after at least 5 years of treatment discontinuation),
- •Active HIV, HBV or HCV infection,
- •Positive test results for chronic hepatitis B. All patients must be tested for both HBsAg and HBcAb at screening, if either of the tests is positive, the patient is not eligible for inclusion in the trial. Patients who have protective titers of HBsAb after vaccination are eligible provided they are negative for both HBsAg and HBcAb,
- •Positive testing for hepatitis C (hepatitis C virus [HCV] antibody serology testing). Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA,
- •Vaccination with live vaccines within 28 days prior to start of the preemptive treatment,
- •Known or suspected hypersensitivity to the study medication,
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
Obinutuzumab 1000 mg IV infusion, day: 1, 8, 15, 22
Patients with evidence of MCL molecular relapse defined as an increasing copy number in quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes according to BIOMED-2 methodology and protocols in peripheral blood or/and bone marrow without evidence of clinical relapse/progression after auto-HCT procedure with all inclusion and no exclusion clinical trial criteria will receive 4 weekly infusions of obinutuzumab.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
MRD negativity defined as a MRD level
时间窗: 2 months after obinutuzumab treatment
Molecular response rate (molRR) defined as a rate of molecular response with at least 10-4 sensitivity level assessed by quantitative RQ-PCR
次要结局
- Event-free survival (EFS)(3 years and 2 month)
- Time to relapse/progression(3 years and 2 month)
- Health status measured with EQ-5D from EuroQoL Group(3 years and 2 month)
- Progression-free survival (PFS)(3 years and 2 month)
- Time to molecular relapse(3 years and 2 month)
- Overall survival (OS)(3 years and 2 month)
- Treatment tolerability assessment(3 years and 2 month)