Open-label, Multicenter Phase II Study to Investigate the Efficacy, Safety, and Tolerability of the Bispecific T-cell Engager (BiTE®) MT103 in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 12
- 主要终点
- Percentage of Participants With a Minimal Residual Disease (MRD) Response Within 4 Cycles of Treatment
研究概览
简要总结
The purpose of this study is to determine whether the bispecific T-cell engager (BiTE®) Blinatumomab (MT103) is effective in the treatment of ALL patients with minimal residual disease.
详细描述
The presence of leukemia cells below the cytological detection limit (5% leukemic cells) is defined as minimal residual disease (MRD). If no MRD is detectable (< 10^-4 = less than 1 leukemia cell per 10^4 bone marrow cells) a complete molecular remission is reached. In the last years a series of retrospective studies has shown that MRD in adult ALL is an independent prognostic factor as already demonstrated for childhood leukemia. Diagnostic tools for MRD are polymerase chain reaction (PCR) and/or flow cytometry. PCR analysis can detect fusion transcripts such as bcr/abl and individual clonal rearrangements of immunoglobulins (IgH) and/or T-cell receptor genes (TCR). About 25% of patients with MRD defined by rearrangement comprise a high-risk group with a 94% relapse rate within 3 years. In general for patients with MRD, who are not eligible for allogenic stem cell transplantation, curative treatment is not available. This accounts for MRD defined by the Philadelphia chromosome translocation as well as for MRD defined by rearrangement. The current study is set up to address the question of treating MRD positive ALL with the bispecific anti-cluster of differentiation (CD)19 x anti-CD3 antibody derivative blinatumomab (MT103).
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
- •B-precursor ALL patients in complete hematological remission with molecular failure or molecular relapse starting at any time after consolidation I of front-line therapy within German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) standards or at any time outside GMALL standards.
- •Patients must have a molecular marker for evaluation of minimal residual disease which is either Breakpoint cluster region/gene on human chromosome #9 (Bcr/abl) at any detection level or individual rearrangements of immunoglobulin or T-cell receptor (TCR)-genes measured by an assay with a sensitivity of minimum 10^-4: At least one individual marker at a quantitative level ≥ 10^-
- •Eastern Cooperative Oncology Group (ECOG) Performance Status < 2
- •Ability to understand and willingness to sign a written informed consent
- •Signed and dated written informed consent is available
排除标准
- •Current extra medullar involvement
- •History of or current relevant central nervous system (CNS) pathology (except migraine/headache and/or previous infiltration of cerebrospinal fluid (CSF) by ALL)
- •Current infiltration of cerebrospinal fluid by ALL
- •History of or current autoimmune disease
- •Autologous stem cell transplantation within 6 weeks prior to study entry
- •Any prior allogeneic stem cell transplantation
- •Cancer chemotherapy within 4 weeks prior to study treatment (except for intrathecal prophylaxis and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, steroids)
- •Radiotherapy within 4 weeks prior to study treatment
- •Therapy with monoclonal antibodies (Rituximab, MabCampath) within 6 weeks prior to study treatment
- •Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
- •Presence of human anti-murine antibodies (HAMA)
- •Abnormal bone marrow, renal or hepatic function
- •Indication for a hypercoagulative state
- •History of malignancy other than ALL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or cervix carcinoma in situ
- •Active severe infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator
- •Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)
- •Pregnant or nursing women
- •Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter
结局指标
主要结局
Percentage of Participants With a Minimal Residual Disease (MRD) Response Within 4 Cycles of Treatment
时间窗: Within 4 treatment cycles, 24 weeks
MRD Response is defined as: * If Philadelphia Chromosome (Ph) positive (+) or translocation (t) (4;11), response was achieved when Ph or t(4;11) was below detection limit and individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4. * If Ph and t(4;11) negative, response was achieved when individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4.
次要结局
- Percentage of Participants With an MRD Response After Each Treatment Cycle(At the end of each treatment cycle - Weeks 4, 10, 16, and 22.)
- Time to Hematological Relapse(Up to the data cut-off date of 14 January 2010; maximum duration of follow-up was 564 days.)
- Time to MRD Progression(Up to the data cut-off date of 14 January 2010; Median follow-up time was 155 days)
- Time to MRD Relapse(Up to the data cut-off date of 14 January 2010; Median follow-up time was 116.5 days)
- Change From Screening Value in T-cell Count During Cycle 1(At Screening and in Cycle 1 at the start of infusion, 45 minutes, 2, 6, 12, 24 hours and at Days 2, 7, 14, 21, 28 and 35 after the start of infusion.)
- Serum Cytokine Peak Levels in Cycle 1(Cycle 1 at pre-dose and at post infusion start at 45 minutes; 2, 6, 12, 24, and 48 hours; 7, 14, 21, and 28 days.)
- Number of Participants With Adverse Events(From the start of study treatment until up to 4 weeks after the end of study treatment. The median treatment duration was 87.3 days.)
- Change From Screening Value in B-cell Count During Cycle 1(At Screening and in Cycle 1 at the start of infusion, 45 minutes, 2, 6, 12, 24 hours and at Days 2, 7, 14, 21, 28 and 35 after the start of infusion.)
- Serum Blinatumomab Concentration at Steady State(Cycle 1 at predose and at 2, 6, and 12 hours after start of infusion then weekly until end of the cycle, and at 1, 2, 4, 6, 8, and 24 hours after stop of infusion.)
- Area Under the Drug Concentration-time Curve From Time Zero to Infinity(Cycle 1 at predose and at 2, 6, and 12 hours after start of infusion then weekly until end of the cycle, and at 1, 2, 4, 6, 8, and 24 hours after stop of infusion.)
- Apparent Volume of Distribution(Cycle 1 at predose and at 2, 6, and 12 hours after start of infusion then weekly until end of the cycle, and at 1, 2, 4, 6, 8, and 24 hours after stop of infusion.)
- Clearance of Blinatumomab(Cycle 1 at predose and at 2, 6, and 12 hours after start of infusion then weekly until end of the cycle, and at 1, 2, 4, 6, 8, and 24 hours after stop of infusion.)
- Terminal Half-life of Blinatumomab(Cycle 1 at predose and at 2, 6, and 12 hours after start of infusion then weekly until end of the cycle, and at 1, 2, 4, 6, 8, and 24 hours after stop of infusion.)