Patients with minimal residual disease (MRD) of positive B-precursor acute lymphoblastic leukemia (ALL) MedDRA version: 17.1 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. B–precursor ALL patients in complete hematological remission with molecular failure or molecular relapse starting at any time after consolidation I of front-line therapy within GMALL standards or at any time outside GMALL standards. 2. Patients must have a molecular marker for evaluation of minimal residual disease which is either: - Bcr/abl at any detection level and/or t (4;11) translocation at any detection level messured by reverse transcription - polymerase chain reaction (RT-PCR) - Individual rearrangements of immunoglobulin or TCR-genes measured by an assay with a sensitivity of minimum 10-4: At least one individual marker at a quantitative level equal or greater than 10-4. 3. ECOG Performance Status equal or smaller than 1. 4. Age equal or older than 18 years 5. Ability to understand and willingness to sign a written informed consent 6. 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Current extra medullar involvement 2. History of or current relevant CNS pathology (except migraine/headache and/or previous infiltration of cerebro-spinal fluid (CSF) by ALL, age-related findings such as arteriosclerosis or findings induced by radiation or chemotherapy) 3. Current infiltration of cerebro-spinal fluid by ALL 4. History of or current autoimmune disease 5. Autologous stem cell transplantation within 6 weeks prior to study entry 6. Any prior allogeneic stem cell transplantation 7. Cancer chemotherapy within 4 weeks prior to study treatment (except for intrathecal prophylaxis and/or low dose maintenance therapy such as vincalkaloids, mercaptopurine, methotrexate, steroids) 8. Radiotherapy within 4 weeks prior to study treatment 9. Therapy with monoclonal antibodies (Rituximab, MabCampath) within 6 weeks prior to study treatment 10. Any investigational product within 4 weeks prior to study entry 11. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation 12. Presence of human anti-murine antibodies (HAMA) 13. Abnormal bone marrow function as defined below: - WBC 5 x ULN - Total bilirubin equal or greater than 1.5 x ULN - Creatinine clearance < 50 mL/min determined by the Cockroft-Gould formula. 15. Indication for a hypercoagulative state as defined below: - D-Dimer equal or greater than 2,5 x ULN - Antithrombin activity < 70% 16. Presenc of malignancy other than ALL 17. Active severe infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator 18. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive) 19. Pregnant or nursing women 20. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception dur-ing participation in the study and at least three months thereafter
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of blinatumomab as defined by the effect on minimal residual disease (MRD) ;Secondary Objective: - To assess the effect of blinatumomab on duration of complete hematological remission - To assess the impact of blinatumomab on the level of MRD - To assess the effect of blinatumomab on duration of MRD negativity - To evaluate the safety and tolerability of blinatumomab - To evaluate the pharmacodynamics of blinatumomab - To evaluate the pharmacokinetics of blinatumomab;Primary end point(s): MRD response rate defined by the incidence of MRD negativity within four cycles of treatment with MT103. MRD negativity is defined as bcr/abl below detection limit and/or by individual rearrangements of immunoglobulin or TCR-genes below 10-4.;Timepoint(s) of evaluation of this end point: Incidence of MRD-negativity within 4 cycle´s of blinatumomab treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: - MRD response after any treatment cycle -Time to hematological relapse: First infusion until hematological relapse - Change in MRD level: At the time point of progression - Time to molecular relapse: Period of first detection of MRD-negativity until first detection of MRD-relapse Other endpoints: Evaluation on an ongoing base during the course of the study;Secondary end point(s): - MRD response rate defined by the incidence of MRD negativity after any treatment cycle -Time to hematological relapse - Change in MRD level. MRD progression is defined as the increase in the number of MRD positive cells by one log level as compared to the baseline level, which is equal to a 10-fold increase in the number of MRD positive cells. Progression has to be confirmed within six weeks. The time point of progression is the date of the first measurement. - Time to molecular relapse as defined by the period from the first detection of MRD negativity until the first detection of relapse. Molecular relapse is defined by the detection of bcr/abl, and/or t(4;11) translocation at any level, and/or by the detection of individual rearrangements of immunoglobulin or TCR-genes in =10-4 cells measured by an assay with a sensitivity of minimum 10-4. Molecular relapse has to be confirmed within six weeks. - Overall incidence and severity of adverse events - Quantification and characterization of peripheral blood lymphocytes - Cytokine serum concentrations - Pharmacokinetic parameters: serum half-life, maximum concentration, area under the curve, volume of distribution and clearance of blinatumomab | — |
Countries
Germany
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed