This phase 2 study is designed to evaluate the safety, tolerability and efficacy of allogeneic donor lymphocyte infusions (DLI) combined with the bispecific T cell engager blinatumomab in B-precursor ALL patients who have mixed chimerism (MC) or are MRD-positive after allogeneic SCT and are refractory to at least one MRD- or MC-targeted therapy (i.e. blinatumomab, DLI, tyrosine kinase inhibitors or other agents).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Continuous blinatumomab infusion in combination with allogeneic donor lymphocyte infusion
Klinikum der Universität München
Munich, Germany
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
Subject incidence and grade of adverse events (AEs) including graft-versus-host disease (GvHD). The intensity of (S)AEs will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Time frame: 18 weeks
Efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response
MRD response based on RT-PCR: Complete MRD response (MolCR): hCR and MRD not detectable by molecular probe\[s\] with a sensitivity ≥10-4. The MRD response is calculated as: \[number of patients achieving complete MRD response after at least one cycle (minimum 4 days blinatumomab) of study treatment\] / \[number of patients who received at least 1 cycle (minimum 4 days blinatumomab) of study treatment\]. Mixed chimerism response: CC response: only donor STRs in bone marrow; Low-level MC response ≥90% but \<100% donor STRs in bone marrow. The MC response is calculated as: \[number of patients achieving CC/low-level MC response after at least one cycle (minimum 4 days blinatumomab) of study treatment\] / \[number of patients who received at least 1 cycle (minimum 4 days blinatumomab) of study treatment\].
Time frame: 18 weeks
Duration of the response and survival after combined treatment of DLI and blinatumomab
For patients who received at least one cycle (minimum 4 days of blinatumomab), progression-free survival and overall survival will be calculated using kaplan-meier survival estimates. Descriptive summary statistics (N, mean, standard deviation, minimum, median and maximum) for the duration of response will be performed for all patients with an observed complete MRD response or CC/low-level MC response.
Time frame: 18 weeks
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