NCT04044560终止2 期
Blinatumomab for Minimal Residual Disease (MRD) in Pre-B Cell Acute Lymphoblastic Leukemia Patients Following Hematopoietic Cell Transplantation: A Canadian, Multicentre Trial
适应症
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 6
- 主要终点
- MRD Response
研究概览
简要总结
This is a single arm, open label, multi-centre phase II study using blinatumomab for treatment of detectable minimal residual disease (MRD) in the first year following allogeneic hematopoietic stem cell transplant (HSCT) for patients with B cell acute lymphoblastic leukemia (B-ALL). The study has 2 phases: 1. MRD testing phase and 2. blinatumomab treatment phase. Participants with B-ALL planning for HSCT meeting other eligibility criteria will be enrolled onto the MRD testing phase, which will involve centralized MRD testing of bone marrow aspirate samples on day +56, +100, +180, +270 following HSCT. Participants with detectable MRD ≥10^-4 leukemic cells/total nucleated cells will enroll onto the treatment phase. Blinatumomab treatment will be started following detection of MRD after 7 to 42 days from enrollment onto the treatment phase to allow for initiation of taper of immunosuppressive medications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pre-B-ALL in complete remission (CR), <5% blasts on most recent bone marrow aspirate determined by morphologic assessment, with an intention to proceed to allogeneic HSCT. Eligible participants can be in 1st CR or greater. Presence of detectable MRD by flow cytometry or other techniques in patients that are in morphologic remission prior to transplant is permitted.
- •Detectable MRD measured by flow cytometry or other molecular techniques is acceptable for enrollment in patients with <5% blasts.
- •Patients with either Philadelphia chromosome positive or negative B-ALL are eligible
- •Documented expression of CD19 on the lymphoblast population as measured by flow-cytometry if patient has received prior CD19-directed therapy.
- •Eligibility for HSCT along with conditioning regimen and donor selection will be determined according to the treating centre's policy.
- •Patients must be age ≥1 years and have a baseline performance status of ECOG ≤ 2 (adult) or Lansky ≥ 50% (pediatric).
- •Patient with chronic hepatitis B (Hep B surface antigen or Hep B Core antibody reactive) are eligible if they are receiving treatment to prevent reactivation (e.g. lamivudine, tenofovir) and have undetectable serum Hepatitis B DNA
- •Patients (or legally acceptable designate) must provide written consent.
- •Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study from the time of informed consent signature date until 3 months after completion of study treatment. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
排除标准
- •Inability to comply with study procedures.
- •Active central nervous system (CNS) involvement or other extramedullary disease at the time of enrollment.
- •Uncontrolled infection until resolved.
- •Burkitt lymphoma/leukemia or mixed phenotype leukemia.
- •Chronic infection with Hepatitis C. Previously treated Hepatitis C with undetectable Hepatitis C RNA for six months or longer is acceptable.
- •HIV 1/2 Infection.
- •Treatment Phase of Trial:
- •Inclusion Criteria:
- •Detectable MRD ≥ 10^-4 leukemic cells/TNC on a bone marrow aspirate done on day +56, +100, +180 or day +
- •Morphologic remission on bone marrow from same date (on day +56, +100, +180 or day +270)
- •Patients must be age ≥1 years and have a baseline performance status of ECOG ≤ 2 (adult) or Lansky ≥ 50% (pediatric) documented within 7 days of enrollment.
- •Patients with either Philadelphia chromosome positive or negative B-ALL are eligible
- •Documented expression of CD19 on the lymphoblast population as measured by flow-cytometry if patient has received prior CD19-directed therapy.
- •Patient with chronic hepatitis B (Hep B surface antigen or Hep B Core antibody reactive) are eligible if they are receiving treatment to prevent reactivation (e.g. lamivudine, tenofovir) and have undetectable serum Hepatitis B DNA
- •Adequate organ, liver and renal function including: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), eGFR >30 mL/min/1.73 m, Alkaline phosphatase ≤ 2.5 x ULN, Serum lipase ≤ 1.5 x ULN
- •Patients (or legally acceptable designate) must provide written consent.
- •Exclusion Criteria:
- •Active acute GVHD (grade II-IV) or active moderate-severe chronic GVHD (NIH Grade) at the time of MRD detection are ineligible treatment phase until GVHD resolves or quiescent as determined by the treating physician.
- •Uncontrolled infection until resolved.
- •Chronic infection with Hepatitis C. Previously treated Hepatitis C with undetectable Hepatitis C RNA for six months or longer is acceptable.
- •HIV 1/2 Infection.
- •Extramedullary or CNS disease or the time of MRD detection.
结局指标
主要结局
MRD Response
时间窗: Following 1st cycle of blinatumomab (each cycle is 28 days)
To determine the proportion of patients with MRD response, defined as negative MRD as measured by flow cytometry, after 1 cycle of blinatumomab.
次要结局
- Turnaround time of centralized MRD testing (days)(Through Study Completion, an average of 2 years)
- Survival(Up to 5 years)
- Incidence of MRD Post HSCT(Up to day +270 following stem cell transplant)
- Patient Recruitment (Number of Patients Recruited)(Through Study Completion, an average of 2 years)
- Safety and Tolerability(During Blinatumomab treatment, an average of 24 weeks)
- Time to delivery of blinatumomab following MRD detection(Through Study Completion, an average of 2 years)
研究者
David Sanford
Clinical Assistant Professor
University of British Columbia
研究点 (6)
Loading locations...
相似试验
招募中
1 期
Blinatumomab in Pediatric B-cell Acute Lymphoblastic Leukemia (ALL) With Minimal Residual Disease (MRD)Pediatric ALL, B CellMinimal Residual DiseaseNCT04604691Seoul National University Hospital20
已完成
2 期
Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic LeukemiaChronic Lymphocytic LeukemiaNCT03609593Nicole Lamanna42
已完成
2 期
Blinatumomab for Treatment of R/R or MRD-positive CD19-Positive MPALMixed Phenotype Acute Leukemia (MPAL)Measurable Residual Disease (MRD)NCT04827745University of Maryland, Baltimore2
尚未招募
不适用
Blinatumomab for minimal residual disease before hematopoietic stem cell transplantation in pediatric B-cell precursorKCT0006135Seoul National University Hospital20
已完成
1 期
Blinatumomab & Pembrolizumab for Adults With Relapsed/Refractory B-cell ALL With High Marrow LymphoblastsB-Cell Acute Lymphoblastic Leukemia, AdultNCT03160079University of California, San Diego16