This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in patients with MRD of B- precursor ALL in complete hematological remission including patients with relapse after SCT. The study aims to expand experience generated in previous trials in patients with MRD positive ALL with a focus on additional specific questions.
Transfer of patients to alloHSCT after one cycle or after a subsequent cycle is considered as per protocol discontinuation and as premature treatment discontinuation. In case of hematological or extramedullary relapse, the study treatment will be permanently discontinued. There will be a safety follow-up visit at 30 days after end of the last infusion. There will be efficacy follow-up until 18 months after treatment start. In patients scheduled for SCT the 30-day safety-visit may be performed at the latest time point possible before initiation of subsequent treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Patients will receive blinatumomab at a dose of 28 µg/day as continuous intravenous infusion at constant flow rate for four weeks, followed by a two-week infusion free interval, defined as one treatment cycle. Up to of four cycles will be performed. In case of defined toxicities, the dose of blinatumomab may be reduced to 9µg/day. Patients with an MRD relapse may qualify to receive additional treatment with blinatumomab.
University Hospital of Frankfurt (Main)
Frankfurt am Main, Hesse, Germany
Charité - Campus Benjamin Franklin
Berlin, Germany
MRD response after one cycle
Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT
Time frame: after one cycle of treatment (up to 43 days)
Continuous complete remission
Probability of continuous complete remission (remission duration) at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: 18 months following initiation of blinatumomab
Hematological relapse-free survival
Probability of hematological relapse-free survival rate at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: 18 months following initiation of blinatumomab
Overall survival
Probability of overall survival at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: 18 months following initiation of blinatumomab
Relapse localisations
Frequency of different relapse localisations in proportion to total hematological relapses (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)
Biological evaluation of hematological and extramedullary relapse
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Uniklinik Dresden
Dresden, Germany
Uniklinik Düsseldorf
Düsseldorf, Germany
Univeristätsklinikum Essen
Essen, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, Germany
Universitätsmedizin Göttingen
Göttingen, Germany
Uniklinik Hamburg Eppendorf
Hamburg, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Uniklinik Heidelberg
Heidelberg, Germany
...and 12 more locations
Biological evaluation of hematological and extramedullary relapses including CD19 expression (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)
Serious Adverse Event (SAE) incidence
Overall incidence and severity of adverse events in patients with and without prior SCT (CTCAE 4.0) (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: continuously until End of Safety-Follow-Up (up to 26 weeks)
MRD response after two cycles
Proportion of patients who achieve MRD response after one or two cycles of treatment with Blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: after two cycles of treatment (up to 85 days)
complete MRD response after two cycles
Proportion of patients who achieve complete MRD response after two cycles of treatment with blinatumomab in patients with and without prior SCT (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: after two cycles of treatment (up to 85 days)
duration of MRD response
Probability of continuous MRD response and complete MRD response and duration of MRD response at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: 18 months following initiation of blinatumomab
Time to MRD response
Time to MRD response measured by time-point of first achievement (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: MRD determination after each cycle of treatment (up to 24 weeks)
GvHD
Evaluation of GvHD as part of AE documentation and according to Glucksberg Criteria, grade and localisation. (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: until End of Safety-Follow-Up (up to 26 weeks)
treatment related mortality after subsequent SCT
Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality (at day 100 and later) in patients with SCT in complete remission after blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: after subsequent SCT (at day 100 and later)
treatment related mortality
Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality in patients without SCT in complete remission after blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: continuously until End of Follow-Up (up to 18 Months)
Quality of Life
Measurement of Quality of Life with EORTC instruments (EORTC QLQ C30 and EQ-5D) at different time-points during treatment (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD)
Time frame: until End of Follow-Up (up to 18 Months)