Patients with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor ALL (as defined by I-BFM SG/IntReALL criteria) MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10066109 Term: Precursor B-lymphobla
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * Subjects with Philadelphia (Ph-) chromosome negative high-risk (HR) first relapse B-precursor ALL (as defined by I-BFM SG/IntReALL criteria) * Subjects with M1 or M2 marrow ( 28 days and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: * Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy) Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment. * Abnormal renal or hepatic function prior to start of treatment (day 1) as defined in the 20120215 protocol a. Serum creatinine levels above upper limit of normal, based on the normal ranges for age and gender of the local laboratories b. Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease) * Peripheral neutrophils < 500/µl prior to start of treatment * Peripheral platelets < 50,000/µl prior to start of treatment * Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(s). Procedures required by IntReALL HR guidelines are allowed. * Chemotherapy related toxicities that have not resolved to = grade 2 * 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 * Documented infection with HIV * Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing (excluding asparaginase) * Post-menarchal female subject who is pregnant or breastfeeding, or is planning to become pregnant or breastfeed while receiving protocol-specified therapy and for at least 6 months after the last dose of blinatumomab, or 12 months after the last dose of chemotherapy * Post-menarchal female subject who is not willing to practice true sexual abstinence or use a highly effective form of contraception while receiving protocol-specified therapy and for at least 6 months after the last dose of blinatumomab, or 12 months after the last dose of chemotherapy * Sexually mature male subject who is not willing to practice true sexual abstinence or use a condom with spermicide while receiving protocol-specified therapy and for at least 6 months thereafter. In countries where spermicide is not available, a condom without spermicide is acceptable. * Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-specified therapy and for at least 6 months thereafter * Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject’s and investigator’s knowledge * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. * Placed into an institution due to juridical or regulatory ruling
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate event-free survival (EFS) after blinatumomab when compared to standard of care (SOC) chemotherapy.;Secondary Objective: To evaluate the effect of blinatumomab on overall survival (OS) when compared to SOC chemotherapy • To evaluate reduction in minimal residual disease (MRD) after blinatumomab when compared to SOC chemotherapy • To evaluate the safety of blinatumomab when compared to SOC chemotherapy • To evaluate the safety of allogeneic hematopoietic stem cell transplantation (alloHSCT) after blinatumomab when compared to alloHSCT after SOC chemotherapy •To evaluate the pharmacokinetics (PK) of blinatumomab;Primary end point(s): EFS;Timepoint(s) of evaluation of this end point: from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): *OS *MRD response * Cumulative incidence of relapse * Incidence of adverse events (both serious and non-serious), treatment-related adverse events, adverse events of interest, clinically significant changes in laboratory values * Survival status at 100 days following HSCT * Incidence of anti-blinatumomab antibody formation (blinatumomab arm only) * Pharmacokinetic sampling for blinatumomab concentrations for population PK analysis * Blinatumomab steady-state concentrations;Timepoint(s) of evaluation of this end point: *OS: from time of randomization until the end of the study, or death, whatever comes first . *MRD response: at the end of treatment with investigational product(s) * Cumulative incidence of relapse: from the time of randomization until the date of relapse or M2 marrow after having achieved a CR *Incidence of adverse events (both serious and non-serious), treatment-related adverse events, adverse events of interest, clinically significant changes in laboratory values : during the treatment period *Survival status: at 100 days following alloHSCT * Incidence of anti-blinatumomab antibody formation (blinatumomab arm only): during the whole study * Pharmacokinetic sampling and blinatumomab steady-state concentrations: during the treatment period | — |
Countries
Australia, Austria, Belgium, Brazil, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Turkey, United Kingdom
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed