A Phase II Study of Blincyto in Children With CD19+ Precursor B-lineage ALL and MRD-Positivity Before and/or Following First Allogeneic HSCT
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 14
- 主要终点
- Rate of MRD-negativity
研究概览
简要总结
An add-on phase II trial within the ALL SCTped 2012 FORUM with the primary objective to determine whether the use of Blincyto in paediatric patients with B-lineage ALL and pre- and/or post-transplant MRD could induce MRD-negativity in patients who were MRD-positive before and/or after allogeneic HSCT.
The study protocol entitled "A Phase II Study of Blincyto (Blinatumomab) in Children with CD19+ B-lineage Acute Lymphoblastic Leukemia (ALL) and Minimal Residual Disease (MRD)-Positivity before or following first Allogeneic Hematopoetic Stem Cell Transplantation (HSCT) in complete remission (CR1, CR2, CR3)" was included in the ALL SCTped 2012 FORUM Protocol Appendix 1b.
According to protocol, 15 mcg/m2/day of Blincyto is given in continuous intravenous infusion over a 28-day cycle. Starting day for patients who are MRD-positive before HSCT is between day +60 and day +100 and for patients who become MRD-positive post HSCT it is between day +60 and day +360 post HSCT.
Patients are evaluated for response at day +28 (+4 days) (bone marrow morphology and MRD analysis - defined by PCR/FLOW-techniques) after start of Blincyto-treatment at the end of first Blincyto infusion and at regular post-TX-checks (according to FORUM: days +28, +60, +100, +180 and +360 after HSCT).
The protocol was approved in 10 countries (Austria, Belgium, Czech Republic, Denmark, France, Italy, Norway, Poland, Slovakia and Spain) participating ALL SCTped 2012 FORUM study. Overall, 3 patients were treated with Blincyto (2 in Oslo and 1 in Copenhagen).
However, the Investigator Initiated Research Agreement was terminated by Amgen on 26 April 2022, leading to an early termination of the study, which was approved with the last protocol amendment.
详细描述
6.2.1 Screening / Pretreatment* The screening process begins on the date the subject (or legally acceptable representative) signs the IRB/EC approved ICF and assent form and continues until enrollment. Informed consent and assent must be obtained before completing any study-specific procedures. After written informed consent and assent have been obtained, subjects will be screened in order to assess eligibility for study participation. Only eligible subjects who meet the inclusion/exclusion criteria listed in Section 4 will be enrolled in the study. The total screening window is up to 14 days. If a subject has not met all eligibility criteria at the end of the 14-day window, the subject will be classified as a screen failure on the subject screening log. Subjects who screen fail may be eligible to rescreen one time per Section 6.2.2.
The following assessments/procedures are to be completed during the screening period at time points designated in the Schedule of Assessments:
- Confirmation that the Informed Consent Form and Assent Form have been signed
- Product History Form for subjects who were enrolled in a previous Amgen Blincyto study
- Relevant medical history: including all data which are documented in FORUM trial
- Review of inclusion/exclusion criteria
- Physical examination
- Local laboratory assessments within 7 days prior to treatment start:
- Chemistry
- Coagulation
- Hematology (CBC with differential)
- Bone marrow aspirate (morphological and MRD assessment)
· Lumbar puncture
- Serious Adverse Event reporting 6.2.2 Rescreening* Subjects who are unable to complete or meet eligibility at the initial screening will be permitted to rescreen once, provided study recruitment has not closed. Upon signing a new Informed Consent Form and Assent Form, a new 14-day screening window will begin. Subjects will retain the same subject identification number assigned at the original screening.
After reconsenting, all screening procedures, including the bone marrow aspirate, must be repeated. However, previous bone marrow aspirate/biopsy taken within 14 days of the planned treatment start of Blincyto can be used to determine eligibility.
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
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients participating in ALL SCTped 2012 FORUM;
- •Age: > 0.5 years and < 21 years;
- •B-precursor ALL with < 5% blasts in the bone marrow (M1 bone marrow) and CD19+ minimal residual disease (MRD) before and/or following allogeneic HSCT;
- •Indication for first allogeneic HSCT was CD19+ ALL in first, second or third remission;
- •Allogeneic Hematopoietic Stem Cell Transplant (HSCT): at first dose of Blincyto patients must be at least > 60 days post-SCT and without evidence of grade 2 or higher acute GVHD and off systemic immunosuppression (tapering allowed) and at least 4 weeks after last donor lymphocyte infusion (DLI);
- •Performance-Status (Karnovsky/Lansky): above 50%;
- •Written consent of the parents/legal guardian and, if necessary, the minor patient via "Informed Consent Form";
- •No pregnancy;
- •No secondary malignancy.
排除标准
- •Patients who do not fulfill the inclusion criteria;
- •The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian;
- •Malformation syndromes;
- •Renal impairment (< 30% of normal glomerular filtration rate);
- •Severe pulmonary, hepatic or cardiac impairment due to toxicity or infection (> CTCAE grade 3);
- •Recent episode of seizures or posterior reversible encephalopathy syndrome in the past 30 days;
研究组 & 干预措施
Blincyto
Blincyto is given over a 28-day cycle. Starting day for patients, who are MRD-positive before HSCT is between day +60 and day +100 and for patients, who become MRD-positive post HSCT it is between day +60 and day +360 post HSCT.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Rate of MRD-negativity
时间窗: Patients may receive 2 cycles of treatment. A single cycle of treatment is 28 days (4 weeks) of continuous infusion. Each cycle of treatment is separated by a 14 day (2 weeks) treatment-free interval.
Rate of MRD-negativity is defined as \< 0.01 percent (%) by flow cytometry and \< 10-4 by PCR after first and second Blincyto cycle
次要结局
未报告次要终点
研究者
Prof. Christina Peters
Univ.-Prof. Dr. Christina Peters
St. Anna Kinderkrebsforschung