E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient aged 56 and 74 with CD19 positive, Ph/BCR-ABL negative B-precursor acute lymphoblastic leukemia |
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E.1.1.1 | Medical condition in easily understood language |
Patients with acute lymphoblastic leukemia and aged between 56 and 74 years |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066109 |
E.1.2 | Term | Precursor B-lymphoblastic leukemia acute |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the rate of complete hematologic remission after induction therapy |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <75 years at the time of informed consent* 6. Renal and hepatic function as defined below: - AST (SGOT), ALT (SGPT), and AP < 5 x upper limit of normal (ULN) “(unless related to leukemic liver infiltration by investigator assessment)” - Total bilirubin < 1.5 x ULN (unless related to Gilbert's Meulengracht disease) - Creatinine < 1.5x ULN - Creatinine clearance > 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.
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | 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) |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
18 months following initiation of Blinatumomab |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 26 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Prerequiste for termination of the trial is LVLS (i.e. End of Follow-up-period for the last patient) and completed data collection |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |