ALL SCTped 2012 FORUM Add-on Study Blina Post HSCT

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.

Sex

All

Minimum age

6 Months

Maximum age

21 Years

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;