Patients with minimal residual disease (MRD) positive B-precursor ALL with and without prior SCT documented after an interval of at least 8 days from last systemic chemo-therapy • at a level of =10-4 - <10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 OR • at levels below 10-4 : o Positive <10-4, non quantifiable (MolNE1) OR o Positive <10-4 (MolNE2) OR • Presence of minimal residual disease (MRD), non quantifiable (MolNE3). MedDRA version: 21.1 Leve
Conditions
Sponsors
Goethe-Universität Frankfurt, Universitätsklinikum, Med. Klinik II
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with CD19 positive B–precursor ALL in complete hematological remission defined as less than 5% blasts in bone marrow after at least three intense chemotherapy blocks (e.g., GMALL induction I-II/consolidation I). 2. Presence of minimal residual disease (MRD) after an interval of at least 8 days from last systemic chemo-therapy • at a level of =10-4 - /= 1,000/µL - Platelets >/= 50,000/µL (transfusion permitted) - HB level >/= 9g/dl (transfusion permitted) 5. Renal and hepatic function as defined below: - AST (GOT), ALT (GPT), and AP /= 60 mL/min (e.g. calculated according Cockroft & Gault) 6. Negative HIV test, negative hepatitis B (HbsAg) and hepatitis C virus (anti-HCV) test 7. Negative pregnancy test in women of childbearing potential 8. ECOG Performance Status 0 or 1 9. Age min. 18 years 10. Ability to understand and willingness to sign a written informed consent 11. Signed and dated written informed consent is available 12. Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1. Ph/BCR-ABL positive ALL 2. Presence of circulating blasts or current extramedullary involvement by ALL 3. History or presence of clinically relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome or psychosis) 4. Current detection of ALL blast cells in cerebrospinal fluid 5. History of or active relevant autoimmune disease 6. Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis) 7. Radiotherapy within 4 weeks prior to study treatment 8. Live vaccination within 2 weeks before the start of study treatment 9. Autologous hematopoietic stem cell transplantation (SCT) within six weeks prior to study treatment 10. Allogeneic SCT within 12 weeks before the start of study treatment 11. Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment 12. Any systemic therapy against GvHD within 2 weeks before start of study treatment 13. Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment 14. Treatment with any investigational product within four weeks prior to study treatment 15. Previous treatment with blinatumomab or other anti-CD19-therapy 16. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation 17. History of malignancy other than ALL diagnosed within 5 years prior to start of protocol-specified therapy with the exception of: - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated cervical carcinoma in situ without evidence of disease - Adequately treated breast ductal carcinoma in situ without evidence of disease - Prostatic intraepithelial neoplasia without evidence of prostate cancer 18. Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator 19. Nursing women 20. Woman of childbearing potential and is not willing to use a highly effective method of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment. 21. Male who has a female partner of childbearing potential, and is not willing to use a highly effective form of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of blinatumomab to induce complete MRD response in patients regardless of prior SCT ;Secondary Objective: -Remission duration, relapse-free survival and overall survival -Relapse localisation and relapse characteristics -Efficacy of Blinatumomab in patients with our without prior SCT -Effect of Blinatumomab on MRD response -Safety and tolerability of blinatumomab in patients with or without prior SCT -Effect of blinatumomab on duration of MRD response and complete MRD response -Effect of blinatumomab on the kinetics of MRD response -Effect of blinatumomab on GvHD in patients with relapse after SCT -Outcome of SCT after blinatumomab including mortality rate -Outcome of patients without SCT after blinatumomab -Patient’s quality of life during and after therapy -Effect of pre-defined dose reductions, recommendations and local handling practices, on safety, tolerability and treatment realisation of blinatumomab -Resource utilization and practical treatment organisation -To assess potential biologic predictors of response to blinatumomab and relapse risk after blinatumomab;Primary end point(s): Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT;Timepoint(s) of evaluation of this end point: After one cycle of treatment (4 weeks of treatment), | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints • Probability of continuous complete remission (remission duration) at 18 months following initiation of blinatumomab • Probability of hematological relapse-free survival rate at 18 months following initiation of blinatumomab • Probability of overall survival at 18 months following initiation of blinatumomab • Frequency of different relapse localisations in proportion to total hematological relapses • Biological evaluation of hematological and extramedullary relapses including CD19 expression • Overall incidence and severity of adverse events in patients with and without prior SCT (CTC-AE 4.0) • Proportion of patients who achieve MRD response after one or two cycles of treatment with Blinatumomab • Proportion of patients who achieve complete MRD response after two cycles of treatment with blinatumomab in patients with and without prior SCT • Probability of continuous MRD response and complete MRD response and duration of MRD response at 18 months following initiation of blinatumomab • Time to MRD response measured by time-point of first achievement • Evaluation of GvHD as part of AE documentation and according to Glucksberg Criteria, grade and localisa-tion. • 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 • Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality in patients without SCT in complete remission after blinatumomab • 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 Exploratory endpoints • Incidence of dose reductions, incidence of treatment interruptions, days of interruption, withdrawals, total deliver | — |
Countries
Germany
Contacts
Public ContactGMALL-Studienzentrale
Universitätsklinik Frankfurt, Med. Klinik II
Outcome results
None listed