Clinical Trials/2023-506136-32-00

2023-506136-32-00SuspendedPhase 2

A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults and Adolescents with Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) and Minimal Residual Disease Positive (MRD+) B-ALL

Amgen Inc.40 sites in 7 countries58 target enrollmentStarted: October 31, 2025Last updated: August 7, 2026

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Phase 2
Status: Suspended
Sponsor
Enrollment: 58
Locations: 40
Primary Endpoint: Dose escalation - Dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAE), serious TEAE, treatment-related TEAE , and adverse events of interest.

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

Brief Summary

Dose escalation - Evaluate the safety and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)

Dose escalation - Determine the maximum tolerated dose (MTD) and preliminary recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab

Dose Expansion - Evaluate the efficacy of SC blinatumomab

Phase 2 Ph-IIC (Subcutaneous Formulation 1 [SC1] and Subcutaneous Formulation 2 [SC2] Cohorts)a,b - Evaluate the PK following SC administration of SC1 and SC2 blinatumomab formulations

Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - Evaluate the efficacy of SC blinatumomab

Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - Evaluate the efficacy of SC blinatumomab

Study Design

Allocation: Na
Primary Purpose: Phase 2 Part
Masking: None

Eligibility Criteria

Ages: 0 years to 65+ years (0-17 Years, 18-64 Years, 65+ Years)
Accepts Healthy Volunteers: No

Inclusion Criteria

•101 Subject has provided informed consent before initiation of any study specific activities/procedures and/or the subject’s legally authorized representative has provided informed consent prior to any study specific activities/procedures being initiated 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 or the subject’s legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated.
•(Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 105 Relapsed B precursor ALL at any time after allogeneic HSCT.
•(Disease Status) 106 Ph IIR, Ph IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the BM per local assessment.
•107 Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
•114 (Age requirement) Ph-IIRa and Ph-IIMa: Age ≥ 17 years at time of informed consent.
•113 (Age requirement) Ph-IIRb and Ph-IIMb: Age ≥ 12 years and <17 years at time of informed consent.
•107 (Performance Status Requirement) Age ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
•115 (Performance Status Requirement) Age 16 to <18 years old: Karnofsky Performance Score ≥ 50%
•116 (Performance Status Requirement) Age < 16 years old: Lansky Performance Score ≥ 50%
•(Disease Status) 117 Ph IIM: Subjects must have B precursor ALL and BMB ≥ 0.01% and <5% per local assessment.
•(Disease Status) 118 Ph IIM: Availability of an appropriate archival bone marrow specimen from initial or relapse diagnosis and the screening BM sample.
•(Disease Status) 108 A Ph+ subject intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) is eligible.
•(Bone Marrow Function) 119 Ph-IIM: Bone marrow function as defined below: • Absolute Neutrophil Count (ANC) ≥500/µL • Platelet count ≥50,000/ µL (transfusion permitted) • Hemoglobin level ≥ 9g/dL (transfusion permitted)
•(Other) 120 Ph-IIRb extended cohort: Weight <45 kg at screening
•109 For subjects in the MRD cohorts only (cohort Ph-IIM), BMB must be <5% and ≥0.1%. This will replace inclusion criterion #106 for subjects in this cohort
•112 Subjects with Isolated (< 5% BMB) Non CNS Extra Medullary Disease (EMD) are eligible in phase 2 cohorts Ph-IIR and Ph-IIM only.
•111 Ph-IIC only: Subject enrolled in SC1 and SC2 comparison cohort (Ph-IIC) must provide consent to participate in the additional PK sample collection requirements.
•102 (Age requirement) Ph-IIC, Dose Escalation and Dose Expansion: Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at time of informed consent.
•Disease status: All subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. For Ph-IIM cohort (subjects with MRD+ ALL [phase 2]) only: Subjects will be eligible for Ph-IIM if they have B-ALL and meet the MRD criteria defined in inclusion criterion #109 below. With the exception of disease status criteria (ie, inclusion criteria #103, #104, #105, #106), Ph-IIM cohort subjects must satisfy all other inclusion criteria to be eligible.
•(Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 103 Subjects with B precursor ALL with any of the following: • Either refractory to primary induction therapy or relapse after or refractory to at least 1 salvage therapy OR • In untreated first, second, third or greater relapse or refractory relapse - First Relapse is defined as achievement of first CR (CR1) during upfront therapy then relapse during or after continuation therapy - Primary Refractory disease is defined as the absence of CR after standard induction therapy - Refractory relapse is defined as lack of CR after salvage treatment - Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage - Refractory to salvage is defined as no attainment of CR after salvage.
•(Disease History) Ph-IIR, Ph IIC, Dose escalation, Dose Expansion: subjects must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility. 104 Relapsed or Refractory B precursor ALL at any time after first salvage therapy

Exclusion Criteria

•Active ALL in the CNS. Presence of > 5 white blood cells (WBC) per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present (confirmed by CSF analysis) and or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
•Isolated EM disease For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts
•Testicular leukemia
•Cancer chemotherapy within 2 weeks before the start of protocolspecified 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 prephase) or pre-phase chemotherapy and/or dexamethasone.
•Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy. Prior failed CD19 directed therapy such as prior blinatumomab or CD19 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 CNS complications (see exclusion criteria 202).
•Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study. Other investigational or observational studies are not permitted while participating in this study
•Dose Escalation, Dose Expansion, Ph IIC: Abnormal screening laboratory values as defined below: - Total bilirubin more than 3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease) - Estimated Creatinine clearance less than 60 mL/min.
•Female subject is pregnant or breastfeeding or planning to become pregnant or donate eggs or breastfeed during treatment and for an additional 96 hours after the last dose of investigational product (SC blinatumomab)
•Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 96 hours after the last dose of investigational product (SC blinatumomab).
•Female subjects of childbearing potential with a positive pregnancy test assessed during Screening by a serum pregnancy test and/or urine pregnancy test.
•Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s awareness. 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
•History or presence of clinically relevant CNS pathology or event such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events (excluding headache) including ICANS from prior CART or other T cell engager therapies.
•Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy.
•Prior failed CD19 directed therapy such as prior blinatumomab or CD19 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 CNS complications
•Ph IIR and Ph IIM: Abnormal screening laboratory values as defined below: - Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease). - Estimated Creatinine clearance < 30 mL/min per the Cockcroft-Gault equation for subjects ≥ 18 years and estimated Glomerular Filtration Rate (eGFR)< 30 mL/min per 1.73 m2 per the Revised Schwartz equation for subjects 12 to < 18 years.
•Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
•Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
•Known hypersensitivity to blinatumomab or to any component of the product formulation.
•Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
•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.
•History of malignancy other than ALL within 3 years prior to start of protocol-specified therapy except for: 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. 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.
•Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy

Arms & Interventions

METHOTREXATE

Auxiliary

Intervention: METHOTREXATE (Drug)

Blinatumomab SC1, Blinatumomab SC2

Test

Intervention: Blinatumomab SC1 (Drug)

Blinatumomab SC1, Blinatumomab SC2

Test

Intervention: Blinatumomab SC2 (Drug)

CYCLOPHOSPHAMIDE

Auxiliary

Intervention: CYCLOPHOSPHAMIDE (Drug)

CYTARABINE

Auxiliary

Intervention: CYTARABINE (Drug)

LEVETIRACETAM

Auxiliary

Intervention: LEVETIRACETAM (Drug)

VINCRISTINE SULFATE

Auxiliary

Intervention: VINCRISTINE SULFATE (Drug)

DEXAMETHASONE

Auxiliary

Intervention: DEXAMETHASONE (Drug)

Outcomes

Primary Outcomes

Dose escalation - Dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAE), serious TEAE, treatment-related TEAE , and adverse events of interest.

Dose expansion - CR/CRh within the first 2 cycles

Phase 2 Ph-IIC (Subcutaneous Formulation 1 [SC1] and Subcutaneous Formulation 2 [SC2] Cohorts) - Blinatumomab PK parameters following SC administration including, but not limited to Cmax, average concentration (Cavg), tmax, and AUC

Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - CR/CRh within the first 2 cycles

Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - CR with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles

Secondary Outcomes

Dose escalation - Blinatumomab PK parameters following SC administration including, but not limited to, minimum concentration over the dosing interval (Cmin), maximum concentration (Cmax), time to maximum concentration (Tmax), area under the concentration-time curve (AUC)
Dose escalation - Complete remission/complete remission with partial hematological recovery (CR/CRh) within the first 2 cycles
Dose escalation - Anti-blinatumomab antibody formation
Dose Expansion and Phase 2 (Ph-IIR and Ph-IIM cohorts) Blinatumomab PK parameters following SC administration including, but not limited to Cmin, Cmax, Tmax, and AUC
Dose Expansion and Phase 2 (Ph-IIR and Ph-IIM cohorts) Anti-blinatumomab antibody formation
Dose Expansion RFS in subjects who achieve response (CR/CRh within the first 2 cycles) is defined as the time from the first achievement of this response until date of the first relapse including extramedullary relapse, or death due to any cause, whichever occurs first
Dose Expansion and Phase 2 (Ph-IIR and Ph-IIM cohorts) Overall survival (OS) is calculated from the time of the start of first dose of SC blinatumomab until death due to any cause
Dose Expansion -Duration of response and RFS is defined as the time from the first onset of response (CR/CRh within the first 2 cycles) until the hematologic relapse (including EM relapse) or death due to any cause, whichever occurs first
Dose Expansion TEAEs, serious TEAEs, treatment related TEAEs, and adverse events of interest
Dose Expansion and Phase 2 (Ph-IIR and Ph-IIM cohorts) Summary scores at each assessment and change from baseline as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ C30)
Phase 2 Ph-IIC (SC1 and SC2 Cohorts) Complete remission/complete remission with partial hematological recovery (CR/CRh) within the first 2 cycles
Phase 2 Ph-IIC (SC1 and SC2 Cohorts) Anti blinatumomab antibody formation
Phase 2 Ph-IIC (SC1 and SC2 Cohorts) RFS in subjects who achieve response (CR/CRh within the first 2 cycles) is defined as the time from the first achievement of this response until date of the first relapse including extramedullary relapse, or death due to any cause, whichever occurs first
Phase 2 Ph-IIC (SC1 and SC2 Cohorts) OS is calculated from the time of the start of first dose of SC blinatumomab until death due to any cause
Phase 2 Ph-IIC (Subcutaneous Formulation 1 [SC1] and Subcutaneous Formulation 2 [SC2] Cohorts) - • Duration of response and RFS is defined as the time from the first onset of response (CR/CRh within the first 2 cycles) until hematologic relapse (including EM relapse) or death due to any cause, whichever occurs first.
Phase 2 Ph-IIC (Subcutaneous Formulation 1 [SC1] and Subcutaneous Formulation 2 [SC2] Cohorts) - TEAEs, serious TEAEs, treatment related TEAEs, and adverse events of interest
Phase 2 Ph-IIC (SC1 and SC2 Cohorts) Summary scores at each assessment and change from baseline as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ C30)
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) (Key Secondary) - • CR within first 2 cycles • CR/CRh/CRi/Blast free hypoplastic or aplastic BM within the first 2 cycles
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) (Key Secondary) • CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) (Key Secondary) • Duration of response and relapse free survival is defined as the time from the first onset of response (CR/CRh within the first 2 cycles) until hematologic relapse (including EM relapse) or death due to any cause, whichever occurs first
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • Duration of molecular response is defined as the time from the first onset of molecular response (CR/CRh with MRD < 10-4 [0.01%] within the first 2 cycles) until hematologic relapse (including EM relapse), molecular relapse (MRD ≥ 10-4) or death due to any cause, whichever occurs first
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • Overall survival (OS) is calculated from the time of the start of first dose of SC blinatumomab until death due to any cause
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • TEAEs, serious TEAEs, treatment-related TEAEs, and adverse events of interest
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - •Blinatumomab PK parameters following SC administration including, but not limited to Cmax Tmax, and AUC for subjects participating in intense PK sampling assessment •Blinatumomab serum concentrations for subjects not participating in intense PK sampling assessment
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • Anti blinatumomab antibody formation
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • Summary scores at each assessment and change from baseline as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQC30) for subjects aged ≥ 17 years at time of assessment and by PedsQL Generic Core Scale for subjects aged 12 to < 17 years at time of consent)
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - •  Proportion of time on treatment with high side effect bother from baseline to end of treatment as measured by Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item for subjects aged ≥ 17 years at time of consent
Phase 2 Ph-IIR (Relapsed/Refractory [R/R] Cohort) - • Pain difference between pain score before and after injection as reported using the Numeric Rating Scale (NRS-11) for subjects aged 12 to <17 years at time of consent)
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) (Key Secondary) - Duration of molecular response is defined as the time from the first onset of molecular response (CR with MRD < 10-4 [0.01%] within the first 2 cycles) until hematologic relapse (including EM relapse), molecular relapse (MRD ≥ 10-4) or death due to any cause, whichever occurs first
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) (Key Secondary) - CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles - CR/CRh/CRi/Blast free hypoplastic or aplastic BM with MRD negative response (MRD <10 4 [0.01%]) within the first 2 cycles
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • RFS is defined as the time from first dose of SC blinatumomab until date of the first hematologic relapse (including EM relapse), or death due to any cause, whichever occurs first
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • OS is calculated from the time of the start of first dose of SC blinatumomab until death due to any cause
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) • TEAEs, serious TEAEs, treatment related TEAEs, and adverse events of interest
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • Anti blinatumomab antibody formation
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • Summary scores at each assessment and change from baseline as assessed by the EORTC QLQC30 for subjects aged ≥ 17 years at time of consent) and by PedsQL Generic Core Scale for subjects aged 12 to < 17 years at time of consent)
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • Proportion of time on treatment with high side effect bother from baseline to end of treatment as measured by FACIT GP5 item for subjects aged ≥ 17 years at time of consent
Phase 2 Ph-IIM (MRD-positive [MRD+] Cohort) - • Pain difference between pain score before and after injection as reported using the Numeric Rating Scale (NRS-11) for subjects aged 12 to < 17 years at time of consent)

Investigators

Sponsor

Amgen Inc.

Sponsor Class

Pharmaceutical company

Responsible Party

Principal Investigator

Medical Information

Scientific

Amgen Inc.

Study Sites (40)

Loading locations...

Similar Trials

Recruiting

Phase 2

A phase 1/2 study of SLN124 in patients with Polycythemia VeraPolycythemia Vera

2023-503544-13-00Silence Therapeutics PLC68

Recruiting

Phase 2

A phase 1/2 study of subcutaneous blinatumomab administration in children with R/R and MRD+ B-ALL

2025-521671-31-00Amgen Inc.5

Not yet recruiting

Phase 1

A Phase IB Trial of Subcutaneous Blinatumomab in Combination With Revumenib for Patients With KMT2A-rearranged Acute Lymphoblastic Leukemia

NCT07283640M.D. Anderson Cancer Center20

Not yet recruiting

Phase 2

Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL+ B-ALL

NCT07301424University of Alberta80

Recruiting

Phase 1

A Phase I Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab

NCT07391670AstraZeneca40