Adult patients with relapsed / refractory B-precursor ALL. MedDRA version: 19.0 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 Ph-negative B-precursor ALL, with any of the following: - relapsed or refractory with first remission duration less than or equal to 12 months in first salvage or - relapsed or refractory after first salvage therapy or - relapsed or refractory within 12 months of allogeneic HSCT 2. 10% or more blasts in bone marrow 3. In case of clinical signs of additional extramedullary disease: measurable disease (at least one lesion = 1.5 cm) 4. Eastern Cooperative Oncology Group (ECOG) performance status = 2 5. Age = 18 years 6. Ability to understand and willingness to sign a written informed consent 7. Signed and dated written informed consent is available 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 176 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: 1. Patients with Ph-positive ALL 2. Patients with Burkitt´s Leukemia according to WHO classification 3. History or presence of clinically relevant CNS pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis 4. Active ALL in the CNS or testes 5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 6. Autologous HSCT within six weeks prior to start of blinatumomab treatment 7. Allogeneic HSCT within three months prior to start of blinatumomab treatment 8. Any active acute Graft-versus-Host Disease (GvHD), or active chronic GvHD Grade 2 – 4 9. Any systemic therapy against GvHD within two weeks prior to start of blinatumomab treatment 10. Cancer chemotherapy within two weeks prior to start of blinatumomab treatment (intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab treatment) 11. Radiotherapy within two weeks prior to start of blinatumomab treatment 12. Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment 13. Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment 14. Treatment with any other investigational medicinal product (IMP) after signature of informed consent 15. Eligibility for allogeneic HSCT at the time of enrollment (as defined by disease status, performance status and availability of donor) 16. Known hypersensitivity to immunoglobulins or to any other component of the IMP formulation 17. Abnormal laboratory values as defined below: a. AST (SGOT) and/or ALT (SGPT) and/or AP = 5 x upper limit of normal (ULN) b. Total bilirubin = 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease) c. Creatinine = 1.5 ULN or Creatinine clearance < 50 ml/min (calculated) d. Hemoglobin (Hb) = 9 g/dl (transfusion allowed) 18. History of malignancy other than ALL within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix 19. Active uncontrolled infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator 20. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive) 21. Pregnant or nursing women 22. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Male patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter 23. Previous treatment with blinatumomab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of blinatumomab in patients with relapsed/refractory B-precursor ALL.;Secondary Objective: - To evaluate safety of blinatumomab in patients with relapsed/refractory B-precursor ALL - To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab - To evaluate CNS symptoms and explore potential predictive factors for CNS events associated with blinatumomab;Primary end point(s): CR (Complete response/remission) + CRh* (Complete response/remission with partial recovery of peripheral blood counts) rate within two cycles of treatment with blinatumomab.;Timepoint(s) of evaluation of this end point: At screening and at the end of each treatment cycle a bone marrow aspiration/biopsy will be performed to evaluate the efficacy of blinatumomab. Following the last treatment cycle, there will be efficacy follow-up visits at three, six, nine, 12, 18 and 24 months after treatment start for patients who did not undergo allogeneic HSCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to hematological relapse (duration of response) 2. Proportion of patients eligible for allogeneic HSCT who undergo the procedure after treatment with blinatumomab 3. CR rate within two cycles of treatment with blinatumomab 4. CRh* rate within two cycles of treatment with blinatumomab 5. PR rate within two cycles of treatment with blinatumomab 6. Relapse-free survival 7. Event-free survival 8. Overall survival 9. Overall incidence and severity of AEs 10. 100-day mortality after allogeneic HSCT 11. Pharmacokinetic parameters: steady state concentration of blinatumomab 12. Serum cytokine concentrations Exploratory endpoints 1. Rate of MRD response within two cycles of treatment with blinatumomab 2. Rate of MRD complete response within two cycles of treatment with blinatumomab 3. Quantification and characterization of peripheral blood lymphocyte subsets 4. Neurological exam abnormalities and changes from baseline;Timepoint(s) of evaluation of this end point: 1. Assessment at the end of each treatment cycle (and optionally at day 15 of the first cycle) and during efficacy follow up (until 24 months after treatment start at most) 2. Until patient´s last follow up (until 3 years after treatment start at most) 3.-5. At the end of the first and second treatment cycle and optionally at day 15 of the first cycle 6.-8. Throughout entire study, until three years after treatment start at most 9. 100 days after HSCT, if applicable 10.-11. At baseline and during the first two treatment cycles Exploratory endpoints 1.-2. At the end of each treatment cycle (and optionally at day 15 of the first cycle) 3. At baseline, during the first two treatment cycles, and during efficacy follow-up (2 years after treatment start at most) 4. Stage 4 of study | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed