Pediatric and adolescent patients with B-precursor ALL in second or later bone marrow relapse, in any marrow relapse after allogeneic HSCT, or refractory to other treatments. 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. Morphologic and immunophenotypic evidence of B-precursor ALL (pro B-, pre B-, common ALL) with > 25% blasts in bone marrow (M3) at study enrolment. 2. Age =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Active acute or extensive chronic GvHD 2. Immunosuppressive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab treatment 3. Evidence for current CNS involvement by ALL (CNS 2, CNS 3) or testicular involvement by ALL [patients with CNS relapse at the time of M3 relapse are not eligible for the Phase I part but are eligible for the Phase II part of the study, if CNS is successfully treated prior to enrollment]. Two successive CSF evaluations at least one week apart following completion of CNS therapy that are CNS1 are required 4. History of relevant CNS pathology or current relevant CNS pathology (seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) 5. History of autoimmune disease with potential CNS involvement or current autoimmune disease 6. Any HSCT within 3 months prior to blinatumomab treatment 7. Cancer chemotherapy within 2 weeks prior to blinatumomab treatment (except for intrathecal chemotherapy and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, glucocorticoids) 8. Chemotherapy related toxicities that haven't resolved to = Grade 2 9. Radiotherapy within 2 weeks prior to blinatumomab treatment 10. Immunotherapy (e.g. rituximab, alemtuzumab) within 6 weeks prior to blinatumomab treatment 11. Any investigational product within 4 weeks prior to study entry 12. Previous treatment with blinatumomab 13. Known hypersensitivity to immune globulins or to any other component of the study drug formulation 14. Presence of HAMA reactivity (in patients with prior exposure to murine antibodies or proteins) 15. Active malignancy other than ALL 16. Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol 17. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive) 18. Pregnant or nursing female adolescent patients 19. Post-menarchal female adolescent patients or male adolescent patients not willing to use an effective form of contraception during treatment phase of the study and at least 3 months thereafter 20. Placed into an institution due to juridical or regulatory ruling
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The first part (Phase I) is to determine the recommended Phase II dose of blinatumomab. The Phase II Part is to assess the efficacy of blinatumomab.;Primary end point(s): Phase I Part: - Maximal tolerable dose defined by = 1 of 6 patients experiencing dose limiting toxicity (DLT) or maximal administered dose (MAD) Phase II Part: - Rate of complete remission (CR) within the first 2 cycles;Secondary Objective: Phase I Part: - To assess the safety of different dose levels of blinatumomab in different age groups - To assess pharmacokinetics of different dose levels of blinatumomab in different age groups - To assess the anti-leukemia activity of blinatumomab - To assess the development of anti-drug antibodies (ADA) to blinatumomab - To describe changes in pharmacodynamic markers following treatment with blinatumomab at differing dose levels Phase II Part: - To assess the safety of blinatumomab - To assess the development of ADA to blinatumomab ;Timepoint(s) of evaluation of this end point: Phase I Part: In the Phase I part of the study, safety will be assessed by the occurence of dose limiting toxicity (DLT) within the first 28 days of treatment (cycle 1). Phase II Part: In the Phase II part of the study, efficacy will be assessed by measurement of complete blood count (CBC) and evaluation of a bone marrow will be assessed at D15 of the first cycle and at the end of the infusion period (D29, can be delayed until Day 42) of every cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I Part: 1. Overall incidence and severity of adverse events 2. Quantification and characterization of pharmacokinetic parameters over time 3. Rate of complete remission (CR) within first 2 cycles 4. Time to hematological relapse 5. CR duration 6. Overall survival (OS) 7. Relapse free survival 8. Proportion of patients who develop ADA at any time 9. Quantification and characterization of cytokine serum concentrations Phase II Part: 1. Overall incidence and severity of adverse events 2. Proportion of patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab 3. Time to hematological relapse 4. CR duration 5. Overall survival (OS) 6. Relapse free survival 7. Proportion of patients who develop ADA at any time Exploratory Endpoints (Phase I + II) 1. Rate of MRD response 2. Rate of complete MRD response;Timepoint(s) of evaluation of this end point: Phase I Part: 1. Continously 2. D1, 3, 8, 15, 22, 29 (cycle 1 + 2) 3.-7. Efficacy will be assessed by measurement of complete blood count (CBC) and evaluation of a bone marrow aspiration at D15 of the first cycle and at the end of the infusion period (D29, can be delayed until Day 42) of each cycle. 8. End of every cycle 9. D1, 2, 3 Phase II Part: 1.-2. Continously 3.-6. as for 3.-7. Phase I Part 7. End of every cycle Exploratory Endpoints (Phase I + II) as for 3.-7. Phase I Part | — |
Countries
Austria, Canada, France, Germany, Italy, Netherlands, Switzerland, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed