Adult patients with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia MedDRA version: 14.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with Philadelphia negative B-precursor ALL, with any of the following: - refractory to primary induction therapy or refractory to salvage therapy, - in untreated first relapse with first remission duration =65 years) yes F.1.3.1 Number of subjects for this age range 92
Exclusion criteria
Exclusion criteria: 1. 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 5 years before enrollment and felt to be at low risk for recurrence by the treating physician - 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. 2. Diagnosis of Burkitt´s Leukemia according to WHO classification 3. History or presence of clinically relevant 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 with the exception of history of CNS leukemia that is controlled with intrathecal therapy 4. Active ALL in the CNS (confirmed by CSF analysis) or testes 5. Isolated extramedullary disease 6. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 7. Autologous HSCT within 6 weeks before the start of protocol-specified therapy 8. Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy 9. Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment 10. Any systemic therapy against GvHD within 2 weeks before start of protocol-specified therapy 11. Known exclusion criteria to investigator choice of SOC chemotherapy (as per product insert). 12. Cancer chemotherapy within 2 weeks before start of protocol-specified therapy (intrathecal chemotherapy and dexamethasone are allowed until start of protocol-specified therapy). In addition, any subject whose organ toxicity (excluding hematologic) from prior ALL treatment has not resolved to no more than CTCAE grade 1 13. Radiotherapy within 2 weeks before the start of protocol-specified therapy 14. Immunotherapy (e.g., rituximab) within 4 weeks before start of protocol-specified therapy 15. Subject received prior anti-CD19 therapy 4.2.16 Abnormal screening laboratory values as defined below: - AST (SGOT) and/or ALT (SGPT) and/or ALP = 5 x upper limit of normal (ULN) - Total bilirubin (TBL) = 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease) - Creatinine = 1.5 ULN or Creatinine clearance < 60 ml/min (calculated) 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. Subject is pregnant or breast feeding, or might become pregnant within 3 months after the last dose of protocol-specified therapy 19. Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving protocol-specified therapy and for an additional 3 months after the last dose of protocol-specified therapy. 20. 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. 21. Male who has a pregnant partner, and is not willing to use a condom during sexual activity while receivin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: evaluate the effect of blinatumomab on overall survival (OS) when compared to standard of care (SOC) chemotherapy;Secondary Objective: • evaluate hematological response induced by blinatumomab when compared to SOC chemotherapy • evaluate event free survival induced by blinatumomab when compared to SOC chemotherapy • evaluate minimal residual disease (MRD) remissions induced by blinatumomab when compared to SOC chemotherapy • estimate the effect of blinatumomab on patient reported outcomes, global health status/quality of life (QoL) using the EORTC QLQ-C30 • evaluate the incidence of allogeneic hematopoietic stem cell transplantation (alloHSCT) and 100-day mortality following HSCT in blinatumomab treated subjects when compared to SOC chemotherapy • evaluate the safety of blinatumomab when compared to SOC chemotherapy Exploratory: • evaluate blinatumomab exposure-response relationships for efficacy and safety;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: Assessment when the 330th death is reported or 12 months after the last subject is randomized, whichever occurs first. If 330 deaths have not been observed 12 months after the last subject is randomized then the primary analysis will occur when at least 300 deaths have been reported in the database (300 deaths provides approximately 80% unconditional power). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoints (in order of hierarchical testing) 1. CR within 12 weeks of treatment initiation 2. CR/CRh*/CRi within 12 weeks of treatment initiation 3. Event Free Survival (EFS) Secondary Efficacy Endpoints 4. Duration of CR 5. Duration of CR/CRh*/CRi 6. MRD remission (defined as MRD level below 10-4 by PCR or flow cytometry) 7. Time to a 10 point decrease from baseline in global health status and QoL scale using EORTC QLQ-C30, or EFS event 8. AlloHSCT with or without blinatumomab treatment Secondary Safety Endpoints 9. Incidence of adverse events 10. 100-day mortality after alloHSCT 11. Incidence of anti-blinatumomab antibody formation 12. Changes in select vital sign and laboratory parameters Exploratory Endpoints 13. Blinatumomab steady state concentration (Css) 14. ALLSS score at measured time points 15. Investigation for mutations in the tumor DNA to predict resistance to blinatumomab treatment;Timepoint(s) of evaluation of this end point: 1+2: after 12 weeks; samples are taken at the end of cycles 1 and 2 3: at the time of relapse, death or EOS 4+5+15: throughout the study; samples are taken at the end of each cycle, at the safety follow-up visit and every 3 months during long-term follow-up 6: at the end of cycles 1 and 2 7+12+14: troughout treatment and at the safety follow-up visit 8+9: throughout the study 10: 100 days after alloHSCT 11: before first dose, after cycle 2 and at the safety follow-up visit 13: day 1 and 15 of cycle 1 | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Ireland, Israel, Italy, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed