A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL

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

The Phase I part of the study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab.

The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease Positive (MRD+) B-ALL in participants 12 years old and greater. It will also conduct a clinical pharmacokinetic (PK) evaluation of SC1 and SC2 blinatumomab formulations.

Study Overview

• Status: Active, not recruiting
• Conditions: B Cell Precursor Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Instituto Alexander Fleming
  • Ciudad Autonoma Buenos Aires, Argentina, C1431FWO
    • Cemic - Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Hospital Italiano de Buenos Aires
  • Córdoba Province
    • Córdoba, Córdoba Province, Argentina, X5000JHQ
      • Sanatorio Allende
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Sydney Childrens Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Childrens Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health, Austin Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6909
      • Perth Childrens Hospital
• Austria
  • Vienna, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
• Belgium
  • Yvoir, Belgium, 5530
    • Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site Godinne
• Brazil
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Hospital Sirio Libanes Brasilia
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-902
      • Instituto Medicina Integral Imip
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hosp de Clinicas de Porto Alegre
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-120
      • Fundacao Amaral Carvalho
    • Ribeirão Preto, São Paulo, Brazil, 14048-900
      • Hosp Clin Fac Med Ribeirao Preto Usp
    • São Paulo, São Paulo, Brazil, 04039-001
      • Instituto Onco Ped Graac Unifesp
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Arthur J E Child Comprehensive Cancer Centre
    • Edmonton, Alberta, Canada, T6G 2P4
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M5G 1E8
      • The Hospital for Sick Children
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100045
      • Beijing Childrens Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Guangzhou, Guangdong, China, 510280
      • Zhujiang Hospital of Southern Medical Unversity
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Jiangsu
    • Suzhou, Jiangsu, China, 215002
      • Children's Hospital of Soochow University
    • Suzhou, Jiangsu, China, 215031
      • The First Affiliated Hospital of Soochow University
  • Shandong
    • Qingdao, Shandong, China, 266003
      • The Affiliated Hospital of Qingdao University
  • Shanxi
    • Xi’an, Shanxi, China, 710061
      • The First Affiliated Hospital Of Xi'An Jiaotong Unversity
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310005
      • The Childrens Hospital, Zhejiang University School of Medicine
• France
  • Le Chesnay, France, 78157
    • Centre Hospitalier de Versailles - Hopital Andre Mignot
  • Lille, France, 59000
    • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
  • Nice, France, 06202
    • Centre Hospitalier Universitaire de Nice - Hopital de l Archet
  • Paris, France, 75010
    • Hopital saint Louis
  • Paris, France, 75019
    • Hopital Robert Debre
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Pierre-Bénite, France, 69645
    • Hôpital Lyon Sud
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer Toulouse Oncopole
• Germany
  • Augsburg, Germany, 86156
    • Universitaetsklinikum Augsburg
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin Berlin, Campus Virchow
  • Berlin, Germany, 12203
    • Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
  • Cologne, Germany, 50937
    • Universitaetsklinikum Koeln
  • Jena, Germany, 07747
    • Universitaetsklinikum Jena
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital, The University of Hong Kong
  • Kowloon Bay, Hong Kong
    • Hong Kong Childrens Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center - Beilinson Hospital
• Italy
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Catania, Italy, 95123
    • Azienda Ospedaliero Universitaria Policlinico G Rodolico - San Marco Presidio Ospedaliero G Rodolico
  • Milan, Italy, 20132
    • Irccs Ospedale San Raffaele
  • Naples, Italy, 80123
    • Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
  • Roma, Italy, 00161
    • Azienda Ospedaliera Policlinico Umberto I
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesù
• Japan
  • Akita
    • Akita, Akita, Japan, 010-8543
      • Akita University Hospital
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukushima
    • Fukushima, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center
    • Yokohami-shi, Kanagawa, Japan, 232-8555
      • Kanagawa Childrens Medical Center
• Mexico
  • Querétaro, Mexico, 76230
    • Health Pharma Queretaro Sa de Cv
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64060
      • Christus Centro de Excelencia en Investigacion
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus Medisch Centrum
  • Utrecht, Netherlands, 3584 CS
    • Prinses Maxima Centrum
• Romania
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof Dr Ion Chiricuta
• South Korea
  • Hwasun-gun, Jeollanam-do, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28009
    • Hospital Universitario Infantil Nino Jesus
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Castille and León
    • Salamanca, Castille and León, Spain, 37007
      • Complejo Asistencial Universitario de Salamanca Hospital Universitario de Salamanca
  • Catalonia
    • Badalona, Catalonia, Spain, 08916
      • Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall D Hebron
    • Esplugues de Llobregat, Catalonia, Spain, 08950
      • Hospital Sant Joan de Déu
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08908
      • Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Hospital Clinico Universitario de Valencia
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Sehir Hastanesi
  • Ankara, Turkey (Türkiye), 06010
    • Saglik Bilimleri Universitesi Gulhane Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey (Türkiye), 34214
    • Bagcilar Medipol Mega Universite Hastanesi
  • Istanbul, Turkey (Türkiye), 34214
    • Istanbul Florence Nightingale Hastanesi
  • Izmir, Turkey (Türkiye), 35575
    • Izmir Ekonomi Universitesi Medical Point Hastanesi
• United States
  • California
    • Clovis, California, United States, 93611
      • University of California San Francisco Fresno at Community Cancer Institute
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C.S. Mott Children's Hospital - University of Michigan
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • New York University Grossman School of Medicine and New York University Langone Hospitals
    • The Bronx, New York, United States, 10467
      • Albert Einstein College of Medicine - Montefiore Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Childrens Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Childrens Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
• Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
• Ph-IIRb and Ph-IIMb: Age ≥ 12 years and < 17 years at time of informed consent.
• Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
• Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
• Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
• Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
• Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and < 5% per local assessment.
• Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
• Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
• Participants aged 16 to < 18 years old: Karnofsky Performance Score ≥ 50%.
• Participants aged < 16 years old: Lansky Performance Score ≥ 50%.
• Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.

• Ph-IIM: BM function as follows:

  • Absolute Neutrophil Count (ANC) ≥ 500/μL
  • Platelet count ≥ 50 000/μL (transfusion permitted)
  • Hemoglobin level ≥ 9 g/dL (transfusion permitted)

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

• Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present 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.
• History or presence of clinically relevant CNS pathology (excluding headache) 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 including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
• Isolated Extramedullary (EM) Disease.
• For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts.
• 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.
• Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
• Testicular leukemia.
• History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
• Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
• Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
• Immunotherapy within 4 weeks before start of protocol-specified therapy.
• Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications.
• Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies).
• Abnormal screening laboratory parameters.
• Female participant: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).

The above is a summary, other exclusion criteria details may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1); Cohorts of at least 3 adult participants with R/R B-ALL will be treated with escalating doses of blinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103
Experimental: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations; 1 cohort of adult participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the preliminary RP2D determined from the dose expansion phase, in participants with R/R B-ALL.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103
Experimental: Ph-IIR: Efficacy of SC Blinatumomab in Participants with R/R B-ALL; The efficacy of SC blinatumomab (in the SC2 formulation) will be evaluated in adults and adolescents with R/R B-ALL.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103
Experimental: Ph-IIM: Efficacy of SC Blinatumomab in Participants with MRD+ B-ALL; The efficacy of SC blinatumomab (in the SC2 formulation) will be evaluated in adults and adolescents with MRD+ B-ALL.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103
Experimental: Dose Expansion Phase: Blinatumomab SC1; Up to 4 cohorts of adult participants with R/R B-ALL will be enrolled at different dose levels to support identification of the RP2D. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.	Drug: Blinatumomab; Blinatumomab will be administered as a subcutaneous (SC) injection.; Other Names: AMG 103

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)	Up to 29 days
Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more serious TEAEs	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs)	Up to approximately 28 weeks
Dose Escalation Phase: Number of participants who experience one or more treatment-related TEAEs	Up to approximately 28 weeks
Dose Expansion and Phase 2 Ph-IIR cohort: Number of participants who achieve complete remission (CR) / complete remission with partial hematological recovery (CRh)	Up to 10 weeks
Phase 2 Ph-IIC cohort: Maximum concentration (Cmax) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Average concentration (Cavg) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIC cohort: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2	Up to approximately 4 weeks
Phase 2 Ph-IIM cohort: Number of participants who achieve CR with MRD-negative response	Up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase, Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants with incidence of anti-blinatumomab antibody formation		Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Overall survival (OS)		Up to approximately 2 years
Dose Expansion Phase and Phase 2 (Ph-IIR cohort and Ph-IIC cohort): Duration of response		Up to approximately 2 years
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Relapse free survival		Up to approximately 2 years
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event		Up to approximately 2 years
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent	The EORTC QLQ-C30 is defined as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.	Baseline (Day 1) up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent		Baseline (Day 1) up to approximately 28 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Summary scores of quality of life at each assessment as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent		Baseline (Day 1) up to approximately 28 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Change from baseline of quality of life as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent		Baseline (Day 1) up to approximately 28 weeks
Phase 2 (Ph-IIR cohort): Number of participants who achieve CR		Up to 10 weeks
Phase 2 (Ph-IIM cohort): Number of participants who achieve CR, CRh, CRi or blast free hypoplastic or aplastic BM with MRD-negative response		Up to 10 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Duration of molecular response		Up to approximately 2 years
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Pain difference between pain score before and after injection as reported using the Numeric Rating Scale (NRS-11) for participants aged 12 to < 17 years at time of consent		Up to approximately 28 weeks
Dose Escalation and Dose Expansion Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab		Up to approximately 10 weeks
Dose Escalation and Dose Expansion Phase: Cmax of blinatumomab		Up to approximately 10 weeks
Dose Escalation and Dose Expansion Phase: Tmax of blinatumomab		Up to approximately 10 weeks
Dose Escalation and Dose Expansion Phase: AUC of blinatumomab		Up to approximately 10 weeks
Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh		Up to 10 weeks
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more TEAEs		Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events		Up to approximately 28 weeks
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more AEIs		Up to approximately 28 weeks
Phase 2 (Ph-IIR cohort): Number of participants who achieve CR, CRh, CRi (complete remission with incomplete hematological recovery) or blast free hypoplastic or aplastic bone marrow (BM)		Up to 10 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Number of participants who achieve CR or CRh with MRD-negative response		Up to 10 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Cmax of blinatumomab for participants participating in intense PK sampling assessment		Up to approximately 4 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Tmax of blinatumomab for participants participating in intense PK sampling assessment		Up to approximately 4 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): AUC of blinatumomab for participants participating in intense PK sampling assessment		Up to approximately 4 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Blinatumomab serum concentrations for participants not participating in intense PK sampling assessment		Up to approximately 4 weeks
Phase 2 (Ph-IIR cohort and Ph-IIM 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 participants aged ≥ 17 years	This endpoint applies to participants aged ≥ 17 years at time of consent.	Baseline (Day 1) up to approximately 28 weeks

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: BeOne Medicines
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Jabbour E, Zugmaier G, Agrawal V, Martinez-Sanchez P, Rifon Roca JJ, Cassaday RD, Boll B, Rijneveld A, Abdul-Hay M, Huguet F, Cluzeau T, Diaz MT, Vucinic V, Gonzalez-Campos J, Rambaldi A, Schwartz S, Berthon C, Hernandez-Rivas JM, Gordon PR, Bruggemann M, Hamidi A, Chen Y, Wong HL, Panwar B, Katlinskaya Y, Markovic A, Kantarjian H. Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. Am J Hematol. 2024 Apr;99(4):586-595. doi: 10.1002/ajh.27227. Epub 2024 Feb 5.
• Jabbour E, Lussana F, Martinez-Sanchez P, Torrent A, Rifon JJ, Agrawal V, Tormo M, Cassaday RD, Cluzeau T, Huguet F, Papayannidis C, Hernandez-Rivas JM, Rijneveld A, Fleming S, Vucinic V, Boll B, Ikezoe T, Abdul-Hay M, Savoie ML, Schuh AC, Berthon C, Schwartz S, Chiaretti S, Yuda J, Miyazaki T, Gonzalez-Campos J, Chen Y, Wong H, Choudhry J, Zugmaier G, Guest E, Gordon P, Kantarjian H. Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial. Lancet Haematol. 2025 Jul;12(7):e529-e541. doi: 10.1016/S2352-3026(25)00144-9. Epub 2025 Jun 15.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Estimated): November 24, 2027
• Study Completion (Estimated): May 25, 2029

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Adolescent; Relapsed; Refractory; Adult; Blinatumomab; Acute lymphoblastic leukemia; Minimal Residual Disease; R/R B-ALL; AMG 103; MRD+ B-ALL
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; blinatumomab
• Other Study ID Numbers: 20180257; 2023-506136-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No