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

NCT04521231 · Amgen
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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 281 participants
Allocation: non_randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2021-01-04
Estimated completion: 2029-05-25
Last updated: 2026-04-16
Interventions
Drug: Blinatumomab
Primary outcomes
  • 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)
Sponsor
Amgen · industry
With: BeOne Medicines
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (102)
City of Hope National Medical CenterRecruiting
Duarte, California, United States
University of Illinois ChicagoRecruiting
Chicago, Illinois, United States
Johns Hopkins UniversityRecruiting
Baltimore, Maryland, United States
C.S. Mott Children's Hospital - University of MichiganRecruiting
Ann Arbor, Michigan, United States
Roswell Park Comprehensive Cancer CenterRecruiting
Buffalo, New York, United States
New York University Grossman School of Medicine and New York University Langone HospitalsRecruiting
New York, New York, United States
Albert Einstein College of Medicine - Montefiore Medical CenterRecruiting
The Bronx, New York, United States
St Jude Childrens Research HospitalRecruiting
Memphis, Tennessee, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
Fred Hutchinson Cancer CenterCompleted
Seattle, Washington, United States
The Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Hospital Italiano de Buenos AiresRecruiting
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Sanatorio AllendeRecruiting
Córdoba, Córdoba Province, Argentina
Instituto Alexander FlemingRecruiting
Buenos Aires, Argentina
Cemic - Centro de Educacion Medica e Investigaciones Clinicas Norberto QuirnoRecruiting
Ciudad Autonoma Buenos Aires, Argentina
Sydney Childrens HospitalRecruiting
Randwick, New South Wales, Australia
Westmead HospitalRecruiting
Westmead, New South Wales, Australia
Queensland Childrens HospitalRecruiting
South Brisbane, Queensland, Australia
Royal Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
Monash Medical CentreRecruiting
Clayton, Victoria, Australia
Austin Health, Austin HospitalTerminated
Heidelberg, Victoria, Australia
The Alfred HospitalRecruiting
Melbourne, Victoria, Australia
Perth Childrens HospitalRecruiting
Nedlands, Western Australia, Australia
Universitaetsklinikum Allgemeines Krankenhaus WienCompleted
Vienna, Austria
Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site GodinneRecruiting
Yvoir, Belgium
Hospital Sirio Libanes BrasiliaRecruiting
Brasília, Federal District, Brazil
Instituto Medicina Integral ImipRecruiting
Recife, Pernambuco, Brazil
Hosp de Clinicas de Porto AlegreRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Fundacao Amaral CarvalhoRecruiting
Jaú, São Paulo, Brazil
Hosp Clin Fac Med Ribeirao Preto UspRecruiting
Ribeirão Preto, São Paulo, Brazil
Instituto Onco Ped Graac UnifespRecruiting
São Paulo, São Paulo, Brazil
Arthur J E Child Comprehensive Cancer CentreRecruiting
Calgary, Alberta, Canada
University of AlbertaRecruiting
Edmonton, Alberta, Canada
Vancouver General Hospital, Gordon and Leslie Diamond Health Care CentreRecruiting
Vancouver, British Columbia, Canada
The Hospital for Sick ChildrenRecruiting
Toronto, Ontario, Canada
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
Fujian Medical University Union HospitalRecruiting
Fuzhou, Fujian, China
Zhujiang Hospital of Southern Medical UnversityRecruiting
Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical UniversityRecruiting
Guangzhou, Guangdong, China
Henan Cancer HospitalRecruiting
Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and TechnologyRecruiting
Wuhan, Hubei, China
Children's Hospital of Soochow UniversityRecruiting
Suzhou, Jiangsu, China
The First Affiliated Hospital of Soochow UniversityRecruiting
Suzhou, Jiangsu, China
The Affiliated Hospital of Qingdao UniversityRecruiting
Qingdao, Shandong, China
The First Affiliated Hospital Of Xi'An Jiaotong UnversityRecruiting
Xi’an, Shanxi, China
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting
Tianjin, Tianjin Municipality, China
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting
Tianjin, Tianjin Municipality, China
The First Affiliated Hospital of Zhejiang University School of MedicineRecruiting
Hangzhou, Zhejiang, China
Centre Hospitalier de Versailles - Hopital Andre MignotRecruiting
Le Chesnay, France
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude HuriezRecruiting
Lille, France
Centre Hospitalier Universitaire de Nice - Hopital de l ArchetRecruiting
Nice, France
Hopital Saint LouisRecruiting
Paris, France
Hopital Saint AntoineRecruiting
Paris, France
Hopital Robert DebreRecruiting
Paris, France
Hopital Lyon SudRecruiting
Pierre-Bénite, France
Institut Universitaire du Cancer Toulouse OncopoleRecruiting
Toulouse, France
Universitaetsklinikum AugsburgRecruiting
Augsburg, Germany
Charite - Universitaetsmedizin Berlin, Campus Benjamin FranklinRecruiting
Berlin, Germany
Charite - Universitaetsmedizin Berlin, Campus VirchowRecruiting
Berlin, Germany
Universitaetsklinikum KoelnRecruiting
Cologne, Germany
Universitaetsklinikum JenaRecruiting
Jena, Germany
Universitaetsklinikum LeipzigRecruiting
Leipzig, Germany
Universitaetsklinikum TuebingenCompleted
Tübingen, Germany
Universitatsklinikum UlmCompleted
Ulm, Germany
Queen Mary Hospital, The University of Hong KongRecruiting
Hong Kong, Hong Kong
Hong Kong Childrens HospitalRecruiting
Kowloon Bay, Hong Kong
Rambam Medical CenterRecruiting
Haifa, Israel
Azienda Socio Sanitaria Territoriale Papa Giovanni xxiiiRecruiting
Bergamo, Italy
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant OrsolaRecruiting
Bologna, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaRecruiting
Brescia, Italy
Azienda Ospedaliero Universitaria Policlinico G Rodolico - San Marco Presidio Ospedaliero G RodolicoRecruiting
Catania, Italy
IRCCS Ospedale San RaffaeleCompleted
Milan, Italy
Azienda Ospedaliera di Rilievo Nazionale Santobono PausiliponRecruiting
Naples, Italy
Azienda Ospedaliera Policlinico Umberto IRecruiting
Roma, Italy
IRCCS Ospedale Pediatrico Bambino GesuRecruiting
Roma, Italy
Akita University HospitalRecruiting
Akita, Akita, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa-shi, Chiba, Japan
Fukushima Medical University HospitalRecruiting
Fukushima, Fukushima, Japan
Yokohama City University Medical CenterRecruiting
Yokohama, Kanagawa, Japan
Kanagawa Childrens Medical CenterRecruiting
Yokohami-shi, Kanagawa, Japan
Erasmus Medisch CentrumRecruiting
Rotterdam, Netherlands
Prinses Maxima CentrumRecruiting
Utrecht, Netherlands
Institutul Oncologic Prof Dr Ion ChiricutaRecruiting
Cluj-Napoca, Romania
Chonnam National University Hwasun HospitalRecruiting
Hwasun-gun, Jeollanam-do, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
The Catholic University of Korea Seoul St Marys HospitalRecruiting
Seoul, South Korea
Hospital Universitario Virgen del RocioCompleted
Seville, Andalusia, Spain
Hospital Universitario Marques de ValdecillaRecruiting
Santander, Cantabria, Spain
Complejo Asistencial Universitario de Salamanca Hospital Universitario de SalamancaRecruiting
Salamanca, Castille and León, Spain
Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i PujolRecruiting
Badalona, Catalonia, Spain
Hospital Sant Joan de DeuRecruiting
Esplugues de Llobregat, Catalonia, Spain
Institut Catala d Oncologia Hospitalet Hospital Duran i ReynalsRecruiting
L'Hospitalet de Llobregat, Catalonia, Spain
Clinica Universidad de NavarraRecruiting
Pamplona, Navarre, Spain
Hospital Clinico Universitario de ValenciaRecruiting
Valencia, Valencia, Spain
Hospital Universitario Infantil Niño JesusRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Saglik Bilimleri Universitesi Gulhane Egitim ve Arastirma HastanesiRecruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Sehir HastanesiRecruiting
Ankara, Turkey (Türkiye)
Bagcilar Medipol Mega Universite HastanesiRecruiting
Istanbul, Turkey (Türkiye)
Istanbul Florence Nightingale HastanesiRecruiting
Istanbul, Turkey (Türkiye)
Izmir Ekonomi Universitesi Medical Point HastanesiRecruiting
Izmir, Turkey (Türkiye)
A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL · TrialPath