Subjects with treatment-resistant mixed chimerism or MRD of CD19+ B-precursor ALL after allogeneic SCT MedDRA version: 20.0 Level: LLT Classification code 10063621 Term: Acute lymphoblastic leukaemia recurrent System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864
Conditions
Interventions
Trade Name: BLINCYTO
Pharmaceutical Form: Powder for concentrate and solution for solution for infusion
Sponsors
Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients with CD19+ B–precursor ALL (as determined by immunophenotyping) in hCR (defined as having less than 5% blasts in bone marrow) after allogeneic SCT. 2) One, or a combination of the following documented after an interval of at least 2 weeks since cessation of the most recent leukemia-targeting therapy (i.e. chemotherapy, immunotherapy or cellular therapy, except for intrathecal prophylaxis): - Positivity for CD19+ MRD (molecular failure or molecular relapse), defined as presence of MRD at a level of =10-4 according to an assay with a minimum sensitivity of 10-4. - Donor chimerism 30 mL/min. 10) Hepatic function as follows: - Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 3.0 x upper limit of normal (ULN) - Alkaline phosphatase (ALP) =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1) Eligibility for treatment with blinatumomab ALONE or other antibody-based treatment approaches (e.g. inotuzumab ozogamicin), as considered by the treating physician. 2) Eligibility for standard chemotherapy, as considered by the treating physician. 3) Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives (whichever is longer) prior to baseline MRD and/or chimerism assessment. 4) Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment. 5) Any grade of GvHD currently requiring treatment. 6) Clinically relevant central nervous system (CNS) pathology requiring treatment (e.g., unstable epilepsy). 7) Evidence of current CNS involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully controlled prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of combined DLI and blinatumomab treatment in subjects with treatment-resistant MC or MRD of CD19+ B-precursor ALL after allogeneic SCT.;Secondary Objective: 1) To evaluate the efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response. 2) To evaluate the duration of the response and survival ;Primary end point(s): Subject incidence and grade of AEs including GvHD;Timepoint(s) of evaluation of this end point: Safety in terms of AE incidence will be evaluated after the first patient received at least one dose with blinatumomab until LVLS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) For MRD-positive patients: MRD response. Efficacy parameters: complete MRD response rate (patients achieving MolCR, defined as MRD which is not detectable by molecular probes with a sensitivity of =10-4), duration of complete MRD response, and time to complete MRD response. 2) For patients with MC: chimerism response. Efficacy parameters: CC/low-level MC response rate (defined as patients with =90% donor STRs present in bone marrow DNA sample at engraftment analysis), duration of CC/low-level MC response, and time to CC/low-level MC response. 3) Progression-free survival and overall survival. Exploratory Endpoints: 1) Expansion of Donor Lymphocytes as measured by T cell chimerism. 2) Lymphocyte counts as well as T cell activation (including T cell subsets). Other immune subsets may also be examined. 3) Changes in serum cytokine levels. 4) CD19 expression levels on the ALL cell surface. 5) Number of blood products transfused during the study period. 6) Days of antibiotic treatment for infection during the study period;Timepoint(s) of evaluation of this end point: Efficacy analysis will be performed on all subjects who received a minimum of 4 days blinatumomab. Endpoints will be analysed by use of appropriate descriptive techniques after the EOCS visit has been completed by all subjects. | — |
Countries
Germany
Contacts
Public ContactStudienzentrale Hämatologie
Klinikum der Universität München
Outcome results
None listed