BLINATUMOMAB for B-cell precursor acute lymphoblastic leukaemia (relapsed/refractory) | Minimal residual disease (MRD) positive B-cell precursor acute lymphoblastic leukaemia

Inclusion criteria

• {"criterion_text":"- Participant’s legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent, and the participant has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated."}
• {"criterion_text":"- Age 28 days to < 12 years at the time of consent"}
• {"criterion_text":"- Lansky Performance Status (LPS) of ≥ 50%"}
• {"criterion_text":"- Prior CD19-directed therapy such as blinatumomab or CD19 chimeric antigen receptor T cells (CAR-T) cells will be allowed (with demonstrated continued CD19+ expression) if treatment ended >4 weeks prior to start of protocol therapy and no prior central nervous system (CNS) complications (see CNS exclusion criteria below)."}
• {"criterion_text":"- Any Philadelphia chromosome-positive (Ph+) participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible."}
• {"criterion_text":"- For Phase 1b and Phase 2 cohort in participants with R/R B-ALL (Ph2-R): Participants with B-ALL relapsed after or refractory to any line of treatment including allogeneic HSCT  Refractory disease is defined as the failure to achieve CR.  Relapsed disease is defined as isolated hematological relapse or combined hematological and extramedullary (EM) relapse after achieving a CR. Greater than or equal to 5% blasts in the BM is considered as relapse in the BM."}
• {"criterion_text":"- For Phase 2 cohort in participants with MRD+ B-ALL (Ph2-M): Participants with MRD+ B-ALL must have between ≥ 0.1% and < 5% blasts in the BM. With a peripheral blood count as defined below: ANC (neutrophils) ≥ 500/μL; Platelets ≥ 50,000/μL (transfusion permitted)"}
• {"criterion_text":"- For Phase 2 cohort in participants with MRD+ B-ALL (Ph2-M):Submission of an archival bone marrow specimen from primary diagnosis or relapse for clone-specific calibration of MRD. See section 8.2.9 and the lab manual for minimum sample requirements. For patients in the US and Canada that have a prior Adaptive clonoSEQ result from bone marrow testing that can be made available for use in this study for clone specific calibration, this may be acceptable in lieu of the archival bone marrow specimen with approval by the Medical Monitor. The participant must also provide consent to the use of the prior clonoSEQ result."}

Exclusion criteria

• {"criterion_text":"- Disease Related: Active ALL in the CNS. If CSF leukemia is present, participants must receive intrathecal therapy and have documented negative CSF prior to enrolling."}
• {"criterion_text":"- Prior/Concomitant Therapy: 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"}
• {"criterion_text":"- Prior/Concomitant Therapy: Allogeneic HSCT within 12 weeks before the start of blinatumomab"}
• {"criterion_text":"- Prior/Concomitant Therapy: Cancer chemotherapy within 2 weeks before the start of protocol specified therapy, with the exception of intrathecal chemotherapy and/or low dose maintenance therapy (for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea). Any low dose chemotherapy as stated above must be discontinued before starting pre-phase chemotherapy and/or dexamethasone."}
• {"criterion_text":"- Prior/Concomitant Therapy: Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol specified therapy"}
• {"criterion_text":"- Prior/Concurrent Clinical Study Experience: Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment in another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies."}
• {"criterion_text":"- Diagnostic Assessments: Abnormal screening laboratory values as defined below: Direct bilirubin > 3.0 mg/dL prior to start of treatment; Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min. per 1.73 m2 per the Revised Schwartz equation for children 2 to < 12 years. For children < 2 years of age, at least 50% of age and gender appropriate normal"}
• {"criterion_text":"- Other Exclusions: Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the Participant, Participant’s legal guardian’s, and investigator’s knowledge. Completion of patient reported outcomes questionnaires is not required and will not be prohibitive to enrollment in case patient has intellectual disability or cognitive impairment or in case instrument is unavailable in subject’s language."}
• {"criterion_text":"- History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures or completion. Completion of patient reported outcomes questionnaires is not required and will not be prohibitive to enrollment in case patient has intellectual disability or cognitive impairment or in case instrument is unavailable in subject’s language."}
• {"criterion_text":"- Other Medical Conditions: History of other malignancy within the past 3 years, with the following exception: Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician."}
• {"criterion_text":"- Other Medical Conditions: History or presence of clinically relevant CNS pathology or event such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or severe (≥ grade 3) CNS events including ICANS from prior CAR-T or other T-cell engager therapies."}
• {"criterion_text":"- Other Medical Conditions: Isolated EMdisease"}
• {"criterion_text":"- Other Medical Conditions: Current autoimmune disease or history of autoimmune disease with potential CNS involvement."}
• {"criterion_text":"- Other Medical Conditions: Patients with Down Syndrome are not eligible for this study"}
• {"criterion_text":"- Prior/Concomitant Therapy: Known hypersensitivity to blinatumomab or to any component of the product formulation. Sensitivity to any of the products administered during dosing."}
• {"criterion_text":"- Prior/Concomitant Therapy: Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication."}
• {"criterion_text":"- Prior/Concomitant Therapy: Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus."}

Primary endpoints

• {"endpoint_text":"- Phase 1b: Dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAE), serious TEAE, treatment related TEAE, and adverse events of interest (EOI)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 R/R B-ALL (Cohort Ph2-R): CR/CRh within the first 2 cycles","definition_or_measurement_approach":"CR/CRh measured within the first 2 cycles (as stated)."}
• {"endpoint_text":"- Phase 2 MRD+ B-ALL (Cohort Ph2-M): CR with MRD negative response (MRD <10-4 [0.01%]) within the first 2 cycles","definition_or_measurement_approach":"MRD negative defined as MRD < 10^-4 (0.01%); CR with MRD negative response assessed within first 2 cycles."}

Secondary endpoints

• {"endpoint_text":"- Phase 1b: Complete remission/complete remission with partial hematological recovery (CR/CRh) within the first 2 cycles","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 1b: CR within the first 2 cycles","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 1b: CR/CRh/CRi/Blast free hypoplastic or aplastic BM within the first 2 cycles","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 1b: MRD negative response (MRD level < 10-4 [0.01%]) within the first 2 cycles","definition_or_measurement_approach":"MRD negative defined as MRD < 10^-4 (0.01%) within first 2 cycles."}
• {"endpoint_text":"- Phase 1b: DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including EM relapse) per investigator’s assessment or death due to any cause, whichever occurs first","definition_or_measurement_approach":"DOR = time from first CR/CRh response within first 2 cycles until hematological relapse (including EM relapse) per investigator assessment or death."}
• {"endpoint_text":"- Phase 1b: PK parameters following SC blinatumomab administration including, but not limited to, maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the concentration time curve (AUC)","definition_or_measurement_approach":"PK parameters measured post-dose (Cmax, Tmax, AUC as listed)."}
• {"endpoint_text":"- Phase 1b: Incidence of anti-blinatumomab antibody formation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R) Key Secondary: CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles","definition_or_measurement_approach":"MRD negative defined as MRD < 10^-4 (0.01%); CR/CRh with MRD negative response assessed within first 2 cycles."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R) Key Secondary: DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including EM relapse) per investigator’s assessment or death due to any cause, whichever occurs first","definition_or_measurement_approach":"DOR = time from first CR/CRh response within first 2 cycles until hematological relapse (including EM relapse) per investigator assessment or death."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): CR within the first 2 cycles","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): CR/CRh/CRi/Blast free hypoplastic or aplastic BM within the first 2 cycles","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): OS is defined as the time from the first dose until death due to any cause","definition_or_measurement_approach":"OS = time from first dose until death due to any cause."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): Incidence of TEAE, serious TEAE, Treatment related TEAE, and EOI","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): Blinatumomab PK serum concentrations","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-R): Incidence of anti-blinatumomab antibody formation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M) Key Secondary: CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles","definition_or_measurement_approach":"MRD negative defined as MRD < 10^-4 (0.01%); CR/CRh with MRD negative response assessed within first 2 cycles."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M) Key Secondary: DOR is defined as the time from the first response CR with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles until hematological relapse (including EM relapse) or MRD relapse (MRD ≥ 10-4 [0.01%]) per investigator’s assessment or death due to any cause, whichever occurs first","definition_or_measurement_approach":"DOR = time from first CR with MRD negative response within first 2 cycles until hematological relapse (including EM relapse) or MRD relapse (MRD ≥ 10^-4) per investigator assessment or death."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M): CR/CRh/CRi/Blast free hypoplastic or aplastic BM with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles","definition_or_measurement_approach":"MRD negative defined as MRD < 10^-4 (0.01%)."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M): OS, defined as the time of the start of first dose of SC blinatumomab until death due to any cause","definition_or_measurement_approach":"OS = time from start of first dose until death due to any cause."}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M): Incidence of TEAE, serious TEAE, Treatment related TEAE, and EOI","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M): Blinatumomab PK serum concentrations","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2 (Cohort Ph2-M): Incidence of anti-blinatumomab antibody formation","definition_or_measurement_approach":""}

Methods

• Physician referral and physician-to-physician (Dr-to-Dr) letters (documented: 'Dr to Dr Letter', 'Physician Referral Letter') targeted to treating clinicians at pediatric oncology/hematology centers (documents listed for multiple Member States).
• GP/primary care communication (document: 'GP Letter') to inform local physicians about the study and referral pathways.
• Website lay summary (document: 'Website Lay Summary_NL') to provide public-facing study information (country/language-specific lay materials).
• Recruitment procedure documentation (K1 recruitment arrangements) describing local recruitment workflow at sites.

Netherlands

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

78

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

149

Number Of Sites

5

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

04-12-2025

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

116

Number Of Sites

4

Number Of Participants

1

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

sponsorDuties codes: [7]; likely data/operational support per dossier entry; contact: customercare@clario.com

Name

Q Squared Solutions Limited

Responsibilities

sponsorDuties codes: [4]; lab/clinical operations support per dossier entry; contact: q2_eu_clinical_trials_information@q2labsolutions.com

Name

Almac Clinical Technologies LLC

Responsibilities

sponsorDuties codes: [3]; IRT/technical support per dossier entry; contact: IRTHELP@almacgroup.com

Name

Veeva Systems Inc.

Responsibilities

sponsorDuties codes: [7]; electronic data capture/CDMS support; contact: CDMS_support@veeva.com

Name

Altasciences Compagnie Inc.

Responsibilities

sponsorDuties codes: [4]; lab/operational support; contact: contact@altasciences.com

Third parties

• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"sponsorDuties codes: [4]; contact: mrdclientmanagers@adaptivebiotech.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact: customercare@clario.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: [4]; contact: q2_eu_clinical_trials_information@q2labsolutions.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: [3]; contact: IRTHELP@almacgroup.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact: CDMS_support@veeva.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact: contact@altasciences.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Amgen Research (Munich) GmbH","duties_or_roles":"sponsorDuties codes: [4]; contact: munich@amgen.de","organisation_type":"Pharmaceutical company"}