Adult patients with relapsed and/or refractory Philadelphia Chromosome- positive B-precursor ALL MedDRA version: 16.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 16.0 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. Patients with Ph+ B-precursor ALL, with any of the following: • Relapsed or refractory to at least one second generation TKI (dasatinib, nilotinib, bosutinib, ponatinib) OR intolerant to second generation TKI and intolerant or refractory to imatinib mesylate 2. Greater than 5% blasts in bone marrow 3. Eastern Cooperative Oncology Group (ECOG) performance status = 2 4. Age = 18 years of age, at the time of informed consent 5. Subject has provided informed consent or subject’s legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent. 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 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. History of malignancy other than ALL within 5 years prior to start of protocol-required 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. History or presence of clinically relevant CNS pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis - With the exception of CNS leukemia that is well controlled with intrathecal therapy 3. Active ALL in the CNS (confirmed by CSF analysis) or testes (no clinical sign thereof) 4. Isolated extramedullary disease 5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 6. Allogeneic HSCT within 12 weeks prior to start of blinatumomab 7. Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment 8. Any systemic therapy against GvHD within 2 weeks prior to start of blinatumomab 9. Cancer chemotherapy within 2 weeks prior to start of blinatumomab (intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab). In addition, any subject whose organ toxicity (excluding hematologic) from prior ALL treatment has not resolved to no more than CTCAE grade 1. 10. Immunotherapy (eg, rituximab) within 4 weeks prior to start of blinatumomab 11. Subject received prior anti-CD19 therapy 12. Eligibility for alloHSCT at the time of enrollment (as defined by disease status, performance status and availability of donor) 13. Abnormal screening laboratory values as defined below: - AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase = 5 x upper limit of normal (ULN) - Total bilirubin = 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease) - Creatinine = 1.5 ULN or creatinine clearance < 60 mL/min (calculated) 14. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive). 15. Subject is pregnant or breast feeding, or might become pregnant within 3 months after the last dose of protocol-specified therapy 16. Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving blinatumomab and for an additional 3 months after the last dose of protocol-specified therapy 17. Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception for at least an additional 3 months after the last dose of protocol-specified therapy 18. Male who has a pregnant partner, and is not willing to use a condom during sexual activity for 3 months after the last dose of protocol-specified therapy 19. 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). The 30 days is calculated from day 1 of bli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary objectives: • To evaluate the rate of Minimal Residual Disease (MRD) remission in adult subjects with R/R Ph+ B-precursor ALL • To evaluate other measures of efficacy of blinatumomab in adult subjects with R/R Ph+ B-precursor ALL • To estimate the safety of blinatumomab in adult subjects with R/R Ph+ B-precursor ALL • To evaluate pharmacokinetics (PK) of blinatumomab in adult subjects with R/R Ph+ B-precursor ALL Exploratory Objectives: • To evaluate the duration of MRD response • To evaluate the efficacy of blinatumomab against specific bcr-abl mutations;Primary end point(s): CR/CRh* rate within 2 cycles of treatment with blinatumomab;Timepoint(s) of evaluation of this end point: Assessment at the end of the first and second treatment cycle;Main Objective: To evaluate the rate of complete remission/complete remission with partial hematological recovery (CR/CRh*) in adult subjects with Relapsed/Refractory (R/R) Philadelphia Chromosome Positive (Ph+) B-precursor Acute Lymphoblastic Leukemia (ALL) who receive blinatumomab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: 1. Rate of MRD remission within 2 cycles of treatment with blinatumomab 2. Duration of CR or CRh* 3. CR rate within 2 cycles of treatment with blinatumomab 4. CRh* rate within 2 cycles of treatment with blinatumomab 5. CR+CRh*+ Complete Response incomplete (CRi) rate within 2 cycles of treatment with blinatumomab 6. Overall survival 7. Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) and 100-day mortality after alloHSCT 8. Incidence of adverse events and antibody formation 9. Pharmacokinetic parameters: Serum concentration of blinatumomab Exploratory Endpoints: 1. Duration of MRD Remission with blinatumomab treatment 2. Efficacy of blinatumomab against specific bcr-abl mutations;Timepoint(s) of evaluation of this end point: Secondary Endpoints: 1+3+4+5: Assessment at the end of the first and second treatment cycle 2: Assessment at the end of each treatment cycle, 30 days after last dose (safety follow-up) and up to 18 months long-term follow-up (every 3 months) 6: Assessment throughout entire study including treatment, 30 days safety follow-up and up to 18 months long-term follow-up 7: Assessment throughout entire study and 100 days after alloHSCT 8: Assessment throughout treatment period and 30 days after last dose (safety follow-up) 9: Assessment at day 8 of cycle1 and day 1 of cycle 2 Exploratory Endpoints: 1+2: Assessment at the end of each treatment cycle, 30 days after last dose (safety follow-up) and up to 18 months long-term follow-up (every 3 months) | — |
Countries
France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed