Patient aged 56 and 74 with CD19 positive, Ph/BCR-ABL negative B-precursor acute lymphoblastic leukemia MedDRA version: 21.1 Level: LLT Classification code 10066109 Term: Precursor B-lymphoblastic leukemia acute System Organ Class: 100000004864
Conditions
Sponsors
Goethe Universität Frankfurt
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Newly diagnosed patients with CD19 positive B–precursor ALL 2. Greater than 25% blasts in the bone marrow 3. Eastern Cooperative Oncology Group (ECOG) performance status = 2 4. Charlson comorbidity score = 2 5. Age >55 and 50 mL/min (e.g. calculated according Cockroft & Gault) 7. Negative pregnancy test in women of childbearing potential 8. Ability to understand and willingness to sign a written informed 9. For Germany: Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL) * in patients aged 75-76 years fulfilling all inclusion criteria without exclusion criteria and without relevant comorbidities the decision on inclusion can be discussed on an individual basis with the study coordination. 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Antileukemic pretreatment (GMALL prephase with dexamethasone and cyclophosphamide allowed) 2. History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of: - Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician including - 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. 3. History or presence of clinically relevant (per investigator's assessment) CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis 4. Active ALL in the CNS (confirmed by CSF analysis) or testes (clinical diagnosis) or other extramedullary involvement; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted. 5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 6. Known exclusion criteria to recommended chemotherapy 7. Known positivity of HIV, hepatitis B (HbsAG) or hepatitis C virus (anti-HCV) 8. Subject received prior anti-CD19 therapy 9. Live vaccination within 2 weeks before the start of study treatment 10. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation - Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study(s). Thirty days is calculated from day 1 of protocol-specified therapy - Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing. - Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject and Investigator’s knowledge. - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. - 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. - Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 3 months after the last dose of protocol-specified therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the rate of complete hematologic remission after induction therapy;Secondary Objective: To evaluate - the rate of complete remission (hematologic and molecular) after induction therapy - Overall survival at 1 year after start of therapy - Early mortality during induction therapy - MRD response rate and complete MRD response rate after induction and consolidation - Duration of MRD response and complete MRD response - Remission duration, relapse (disease) free survival and event-free survival - Role of stem cell transplantation - Relapse localisation - Quality of life of patients during induction and consolidation therapy - Safety and tolerability of induction and consolidation therapy - Treatment realisation (interruptions, dose reductions, treatment discontinuation) - Impact of pre-defined dose reductions and management recommendations ;Primary end point(s): - Proportion of patients achieving a complete hematologic remission after induction therapy defined as one cycle of chemotherapy and one cycle of Blinatumomab - Key-secondary endpoint: Rate of complete hematologic and complete molecular remission (MRD response or complete MRD response) after indution therapy defined as one cycle of chemotherapy and one cycle of Blinatumomab ;Timepoint(s) of evaluation of this end point: After induction therapy defined as one cycle of chemotherapy and one cycle of Blinatumomab (8 weeks of treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: - Probability of overall survival after 1 year - Rate and grade of adverse events (AE) according to CTC-AE in induction Phase I, blinatumomab induction and during CI, CII and CIII with blinatumomab - Proportion of patients who achieve an MRD response or a complete MRD response after induction and consolidation - Time to MRD relapse after prior achievement of MRD response or complete MRD response - Probability of continuous complete remission at 1 year - Probability of relapse free survival at 1 year - Probability of event-free survial at 1 year - Proportion of different relapse localisation in relation to total number of relapses - Quality of life measures (EORTC standard scales) at different time-points during induction and consolidation - Rate and duration of treatment interruptions, dose reductions, mitigation strategies and rate of withdrawals Exploratory endpoints: - Document and analyse hospitalisation time, use of infusion pump systems, use of ambulatory care services - Measurement of biologic markers in bone marrow and peripheral blood throughout induction and consolidation therapy ;Timepoint(s) of evaluation of this end point: 18 months following initiation of Blinatumomab | — |
Countries
Germany
Contacts
Public ContactMedizinische Klinik II
Goethe Universität
Outcome results
None listed