Patients with Relapsed/Refractory B-Precursor acute lymphoblastic leukemia (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 B-precursor ALL relapsed after at least induction and consolidation or having refractory disease a. Relapse is defined as reappearance of disease after CR having at least lasted for 28 days b. Refractory disease is defined as not having achieved CR after induction and/or consolidation I 2. More than 5% blasts in bone marrow 3. ECOG performance status = 2 4. Age = 18 years 5. Life expectancy of = 12 weeks 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. 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 2. Infiltration of cerebrospinal fluid (CSF) and/or testis by ALL 3. History of autoimmune disease with potential CNS involvement or current autoimmune disease 4. Autologous hematopoietic stem cell transplantation (HSCT) within six weeks prior to start of blinatumomab treatment 5. Allogeneic HSCT within three months prior to start of blinatumomab treatment 6. Eligibility for allogeneic HSCT at the time of enrollment (as defined by disease status, performance status and availability of donor) 7. Active Graft-versus-Host Disease (GvHD) 8. Immunosuppressive therapy against GvHD within one week prior to start of blinatumomab treatment 9. Patients with Ph+ ALL eligible for treatment with dasatinib or imatinib 10. Cancer chemotherapy within two weeks prior to start of blinatumomab treatment and TKIs within 72 hours prior to start of blinatumomab treatment (intrathecal prophylaxis and/or steroids (=24 mg/d) are allowed until start of blinatumomab treatment.) 11. Radiotherapy within four 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 product after signature of informed consent 15. Known hypersensitivity to immunoglobulin’s or to any other component of the study drug formulation 16. Presence of human anti-murine antibodies (HAMA) 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 c. Creatinine clearance 1,5 ULN 18. Symptoms or signs of disseminated intravascular coagulation (DIC) 19. 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 20. Active infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator 21. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive) 22. Pregnant or nursing women 23. 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 24. 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 and tolerability of blinatumomab in patients with relapsed/refractory B-precursor ALL. To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab. ;Primary end point(s): CR and CRh* rate within two cycles of treatment with blinatumomab.;Timepoint(s) of evaluation of this end point: the primary endpoint will be analyzed at the completion of the second cycle of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - CR rate. - CRh* rate. - PR rate. - Rate of MRD response (defined as MRD < 10-4) Proportion of patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. - Time to hematological relapse. - Relapse-free survival. - Overall survival (OS). - Overall incidence and severity of adverse events. - Pharmacokinetic parameters: serum half-life, maximum concentration, area under the curve, volume of distribution and clearance of blinatumomab. - Quantification and characterization of peripheral blood leukocyte subsets and serum cytokine concentrations.;Timepoint(s) of evaluation of this end point: the secundary endpoints will bee assessed at the latest five years following initiation of blinatumomab infusion | — |
Countries
Germany
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed