minimal residual disease (MRD) of B-precursor ALL MedDRA version: 20.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Amgen Research (Munich) GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with 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, induction/intensification/ consolidation or three blocks of Hyper CVAD) 2. Presence of minimal residual disease at a level of =10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 documented after an interval of at least 2 weeks from last systemic chemotherapy 3. For evaluation of minimal residual disease, patients must have at least one molecular marker based on individual rearrangements of immunoglobulin or TCR-genes or a flow cytometric marker profile, evaluated by a national or local reference lab approved by the Sponsor 4. Bone marrow or peripheral blood specimen from primary ALL diagnosis /diagnosis of ALL relapse (a sufficient amount of DNA or a respective amount of cell material) for clone-specific MRD assessment must be received by central MRD lab and lab must confirm that the sample is available 5. Bone marrow function as defined in the protocol -ANC (Neutrophile) = 1 000/µL -Thrombozyten = 50,000/µL (transfusion permitted) -HB Level = 9g/dl (transfusion permitted) 6. Renal and hepatic function as defined in the protocol -AST (GOT), ALT (GPT), und AP =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Presence of circulating blasts or current extramedullary involvement by ALL 2. History of relevant CNS pathology or current relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) 3. Current infiltration of cerebrospinal fluid by ALL 4. History of or active relevant autoimmune disease 5. Prior allogeneic HSCT 6. Eligibility for treatment with TKIs (i.e., Philadelphia chromosome-positive (Ph) patients with no documented treatment failure of or intolerance/contraindication to at least 2 TKIs) 7. Systemic cancer chemotherapy within 2 weeks prior to study treatment, (except for intrathecal prophylaxis) 8. Radiotherapy within 4 weeks prior to study treatment 9. Autologous hematopoietic stem cell transplantation (HSCT) within six weeks prior to study treatment 10. Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment 11. Treatment with any investigational product within four weeks prior to study treatment 12. Previous treatment with blinatumomab 13. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation 14. History of malignancy other than ALL within five years prior to treatment start with blinatumomab, with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix 15. 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 16. Nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of blinatumomab to induce complete MRD response ;Secondary Objective: Key secondary objective for patients with Ph-negative ALL • To evaluate the effect of blinatumomab on hematological relapse Other Secondary objectives • To evaluate overall survival in patients with ALL treated with blinatumomab • To evaluate the effect of blinatumomab on the 100d mortality rate associated with allogeneic HSCT • To evaluate the safety and tolerability of blinatumomab • To evaluate the effect of blinatumomab on duration of MRD negativity • To evaluate the effect of blinatumomab on the kinetics of MRD • To evaluate patient’s quality of life during and after therapy • To evaluate resource utilization Exploratory objectives • To assess potential biologic predictors of response to blinatumomab;Primary end point(s): Primary Endpoint: Proportion of patients who achieve complete MRD response defined by absence of MRD after one cycle of treatment with blinatumomab;Timepoint(s) of evaluation of this end point: The primary efficacy assessment will be analyzed at the completion of the first cycle of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoint in patients with Ph-negative ALL • Hematological relapse-free survival rate at 18 months following initiation of blinatumomab Secondary endpoints • Overall Survival • Mortality rate within 100 days after allogeneic HSCT • Time to hematological relapse • Duration of complete MRD response • Effect on MRD level • Overall incidence and severity of adverse events • Patient’s quality of life during and after therapy • Resource utilization;Timepoint(s) of evaluation of this end point: The key secondary endpoint will be assessed at 18 months following initiation of blinatumomab infusion. | — |
Countries
Austria, Belgium, Czech Republic, France, Germany, Italy, Netherlands, Poland, Russian Federation, Spain, United Kingdom
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed