Study Comparing Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care Chemotherapy for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia

Phase 3 Randomized, Controlled Study of Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia With Safety Run-in (Golden Gate Study)

The safety run-in part of the study aims to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The phase 3 part of the study aims to compare event-free survival (EFS) and overall survival (OS) of participants receiving blinatumomab alternating with low-intensity chemotherapy to EFS and (OS) of participants receiving standard of care (SOC) chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Newly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)
• Intervention / Treatment: Drug: Blinatumomab; Drug: Low-intensity chemotherapy regimen; Drug: SOC chemotherapy regimen

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Womens Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra 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
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Bruges, Belgium, 8000
    • AZ Sint-Jan Brugge-Oostende AV
  • Brussels, Belgium, 1200
    • Universite Catholique de Louvain Cliniques Universitaires Saint Luc
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis - Campus Virga Jesse
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege - Sart Tilman
  • Roeselare, Belgium, 8800
    • AZ Delta Campus Rumbeke
  • Yvoir, Belgium, 5530
    • Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site Godinne
• Brazil
  • Rio de Janeiro, Brazil, 22640-000
    • Hemorio
  • São Paulo, Brazil, 01246-000
    • Instituto Cancer Sao Paulo Icesp
  • Federal District
    • Brasília, Federal District, Brazil, 70335-902
      • Igesd Instituto de Gestao Estrategica da Saude do Distrito Federal
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • Hospital das Clinicas da Universidade Federal de Goias
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Hospital 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 Jose Do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
• Bulgaria
  • Plovdiv, Bulgaria, 40002
    • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Sofia, Bulgaria, 1797
    • Specialized Hospital for Active Treatment of Hematology Diseases EAD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3H 0V9
      • Cancer Care Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Queen Elizabeth II, Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Hospital and Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • CEMTL Hopital Maisonneuve Rosemont
• Chile
  • Santiago, Chile, 7500921
    • Fundacion Arturo Lopez Perez
  • Santiago, Chile, 7580206
    • Inmunocel
  • Santiago, Chile, 7650729
    • Clínica Alemana de Santiago
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Prague, Czechia, 128 20
    • Ustav hematologie a krevni transfuze
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• Estonia
  • Tallinn, Estonia, 13 419
    • North Estonia Medical Centre
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Créteil, France, 94010
    • Hopital Henri Mondor
  • Dijon, France, 21000
    • Centre Hospitalier Universitaire de Dijon - Hopital du Bocage
  • Le Chesnay, France, 78157
    • Centre Hospitalier de Versailles - Hopital Andre Mignot
  • Lille, France, 59000
    • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44000
    • Centre Hospitalier Universitaire de Nantes - Hopital Hotel Dieu
  • Nice, France, 06202
    • Centre Hospitalier Universitaire Archet 2
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Pessac, France, 33604
    • Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque
  • Pierre-Bénite, France, 69645
    • Hôpital Lyon Sud
  • Rennes, France, 35000
    • Centre Hospitalier Universitaire de Rennes
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
• Germany
  • Augsburg, Germany, 86156
    • Universitaetsklinikum Augsburg
  • Berlin, Germany, 12203
    • Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
  • Dresden, Germany, 01307
    • Universitaetsklinikum Dresden
  • Düsseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Jena, Germany, 07747
    • Universitaetsklinikum Jena
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein - Kiel
  • München, Germany, 81377
    • Klinikum der LMU Muenchen
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital of Athens
  • Athens, Greece, 10676
    • Evangelismos Hospital
  • Athens, Greece, 12462
    • Attiko General University Hospital
  • Heraklion, Greece, 71500
    • University Hospital of Heraklion
  • Ioannina, Greece, 45500
    • University Hospital Of Ioannina
  • Larissa, Greece, 41110
    • University Hospital of Larissa
  • Pátrai, Greece, 26504
    • University Hospital of Patras
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki Georgios Papanikolaou
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital, The University of Hong Kong
  • Kowloon, Hong Kong
    • Princess Margaret Hospital
  • New Territories, Hong Kong
    • Tuen Mun Hospital
• Hungary
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem
  • Budapest, Hungary, 1097
    • Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Eger, Hungary, 3300
    • Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház Nyíregyházi Jósa András Tagkórház
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center - Beilinson Hospital
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino IRCCS
  • Lecce, Italy, 73100
    • Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
  • Mestre (VE), Italy, 30174
    • Azienda Unità Locale Socio Sanitaria 3 Ospedale Dell Angelo
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Naples, Italy, 80131
    • Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
  • Perugia, Italy, 06156
    • Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia
  • Pescara, Italy, 65124
    • Azienda Unita Sanitaria Locale Pescara Ospedale Civile Santo Spirito
  • Roma, Italy, 00161
    • Azienda Ospedaliera Policlinico Umberto I
  • Torino, Italy, 10126
    • Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo Roma
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital
  • Akita
    • Akita, Akita, Japan, 010-8543
      • Akita University Hospital
  • Chiba
    • Kamogawa-shi, Chiba, Japan, 296-8602
      • Tesshokai Kameda General Hospital
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital
    • Kurume-shi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Fukushima
    • Fukushima, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital
  • Gunma
    • Maebashi, Gunma, Japan, 371-0821
      • Gunma Saiseikai Maebashi Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0006
      • Sapporo Hokuyu Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Kanagawa
    • Isehara-shi, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Nagasaki
    • Nagasaki, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 701-1192
      • National Hospital Organization Okayama Medical Center
  • Osaka
    • Osaka, Osaka, Japan, 545-8586
      • Osaka Metropolitan university Hospital
    • Sakai-shi, Osaka, Japan, 590-0197
      • Kindai University Hospital
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Metropolitan Komagome Hospital
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
  • Yamagata
    • Yamagata, Yamagata, Japan, 990-9585
      • Yamagata University Hospital
• Mexico
  • Huixquilucan, Mexico, 52787
    • Hematologica Alta Especialidad
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Mexico City
    • Mexico City, Mexico City, Mexico, 01120
      • Boca Clinical Trials Mexico SC
    • Mexico City, Mexico City, Mexico, 01330
      • Centro Oncologico Internacional
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr Jose Eleuterio Gonzalez
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
• Portugal
  • Coimbra, Portugal, 3004-561
    • Unidade Local de Saude de Coimbra, EPE
  • Lisbon, Portugal, 1099-023
    • Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE
  • Lisbon, Portugal, 1649-035
    • Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
  • Lisbon, Portugal, 1169-050
    • Unidade Local de Saude de Sao Jose, EPE - Hospital de Santo Antonio dos Capuchos
  • Porto, Portugal, 4200-072
    • Instituto Português de Oncologia do Porto Francisco Gentil, EPE
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucharest, Romania, 050098
    • Spitalul Universitar de Urgență București
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof Dr Ion Chiricuta
  • Craiova, Romania, 200143
    • Spitalul Clinic Municipal Filantropia Craiova
  • Iași, Romania, 700483
    • Institutul Regional de Oncologie Iasi
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean de Urgenta Sibiu
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny Onkologicky Ustav
  • Bratislava, Slovakia, 851 07
    • Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda
• South Korea
  • Busan, South Korea, 49201
    • Dong-A University Hospital
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daejeon, South Korea, 35015
    • Chungnam National University Hospital
  • Hwasun, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Andalusia
    • Córdoba, Andalusia, Spain, 14004
      • Hospital Universitario Reina Sofia
    • Seville, Andalusia, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques 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
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08908
      • Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Hospital Universitari i Politecnic La Fe
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 40458
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33305
    • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Şehir Hastanesi
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi
  • Antalya, Turkey (Türkiye), 07025
    • Memorial Antalya Hastanesi
  • Istanbul, Turkey (Türkiye), 34214
    • Bagcilar Medipol Mega Universite Hastanesi
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylul Universitesi Tip Fakultesi Hastanesi
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, NW1 2PG
    • University College London
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Orange, California, United States, 92868-3201
      • University of California Irvine
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Florida
    • Orlando, Florida, United States, 32804
      • Adventist Health System/Sunbelt, Inc d/b/a AdventHealth Orlando
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Hospital, Inc
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Age ≥ 55 years at the time of informed consent. OR

Age 40 to < 55 years of age if at least 1 of the following comorbidities at the time of informed consent:

• history of grades 3 and 4 pancreatitis
• diabetes mellitus with end-organ damage
• severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and aspartate transaminase (AST)/alanine aminotransferase (ALT) > 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy)
• body mass index (BMI) ≥ 40 combined with relevant comorbidities such as metabolic syndrome

• Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older participants in both the experimental and the SOC arm. The participant history will be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.

  • Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score allowed if due to underlying leukemia
  • All participants must have adequate organ function as defined below:
• renal: estimated glomerular filtration rate based on MDRD calculation ≥ 50 mL/min/1.73 m^2
• liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert's Disease or if liver involvement with leukemia); exception for participants 40 to < 55 years of age if they have a comorbidity listed above: severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and AST/ALT > 10 x ULN (liver cirrhosis must be confirmed by biopsy)
• cardiac: left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months). Consult with medical monitor as needed.

Exclusion Criteria:

• Active central nervous system (CNS) leukemia (i.e., CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening.

• History of other malignancy within the past 3 years, with the following exceptions:

  • 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 Note: History of other malignancy (eg, multiple myeloma) treated with immunomodulatory drugs (eg, lenalidomide, thalidomide) in the past 3 years is an exclusion.
  • 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
  • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
• 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, or psychiatric conditions that preclude the use of high dose of corticosteroids
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement
• Known infection with human immunodeficiency virus (HIV)
• Known infection with chronic or active infection with hepatitis B (eg, hepatitis b surface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load) or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected).

Active hepatitis B and C based on the following results:

• positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
• negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll.

• positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll.

  • Participant with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection.
  • Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or optional pre-phase (debulking) chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy; The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety run-in is to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The safety run-in also evaluates a shorter dose step interval from (4 days instead of 7 days) and a 1-week (instead of 2-week) drug free interval between blinatumomab cycles. Blinatumomab will be infused at a lower dose for 4 days and increase to a higher dose on Day 5 of the infusion for the remainder of the infusion.	Drug: Blinatumomab; Continuous intravenous (cIV) infusion; Other Names: Blincyto®; Drug: Low-intensity chemotherapy regimen; Intravenous (IV), oral (PO), subcutaneous (SC), or intrathecal (IT) administration.
Experimental: Phase 3: Blinatumomab alternating with low-intensity chemotherapy; Participants will receive blinatumomab alternating with low-intensity chemotherapy.	Drug: Blinatumomab; Continuous intravenous (cIV) infusion; Other Names: Blincyto®; Drug: Low-intensity chemotherapy regimen; Intravenous (IV), oral (PO), subcutaneous (SC), or intrathecal (IT) administration.
Active Comparator: Phase 3: Standard of care (SOC) chemotherapy; Participants will receive 1 of 2 SOC chemotherapy regimens (GMALL or HyperCVAD) per investigator's choice.	Drug: SOC chemotherapy regimen; Intravenous (IV), oral (PO), subcutaneous (SC), or intrathecal (IT) administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety run-in: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs)	Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest.	Up to approximately 5 years
Phase 3: Overall Survival (OS)	OS is defined as time from randomization (enrollment) until death due to any cause.	Up to approximately 5 years
Phase 3: Event-free Survival (EFS)	Time from randomization (enrollment) until treatment failure, relapse or death from any cause, whichever is earlier. Treatment failure is defined as not achieving a hematological complete CR with MRD response <10-4 by the end of the initial disease assessment period. Relapse is defined as hematologic relapse, extramedullary relapse, and/or molecular relapse (MRD positivity >= 10^-3), whichever occurs earlier, in participants with prior achievement of hematologic CR with MRD response <10^-4. Participants without an event will be censored at their last evaluable disease assessment date.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety run-in: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period		Baseline to Week 14
Safety run-in: Minimal Residual Disease (MRD) Response by the End of Initial Disease Assessment Period	MRD response is defined as the percentage of participants who achieve a response of < 10^-4 measured by polymerase chain reaction (PCR).	Baseline to Week 14
Safety run-in: Relapse-free Survival (RFS)	RFS: In participants who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first.	Up to approximately 5 years
Safety run-in: Steady State Concentration (Css) of Blinatumomab		Up to approximately 34 weeks
Safety run-in: Clearance (CL) of Blinatumomab		Up to approximately 34 weeks
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Fatigue Score	Fatigue score will be measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form 7a.	Baseline to Week 14
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Pain Score	Pain score will be measured by Brief Pain Inventory - Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours.	Baseline to Week 14
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Global Health Status	Global health status will be measured by the Quality of Life Questionnaire (QLQ)-C30 global health status quality of life scale.	Baseline to Week 14
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Physical Function	Physical function will be measured by the QLQ-C30 functional scale.	Baseline to Week 14
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Nausea and Vomiting	Nausea and vomiting will be measured by the QLQ-C30 symptom scale.	Baseline to Week 14
Phase 3: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period		Baseline to Week 14
Phase 3: Minimal Residual Disease (MRD) Response by the End of Initial Disease Assessment Period	MRD response is defined as the percentage of participants who achieve a response of < 10^4 measured by polymerase chain reaction (PCR).	Baseline to Week 14
Phase 3: Relapse-free Survival (RFS)	RFS: In participants who achieve CR, the time from first achievement of this response until the date of the first relapse including hematologic relapse, extra medullary relapse, or death due to any cause, whichever occurs first. Participants without an event will be censored at their last evaluable disease assessment date.	Up to approximately 5 years
Phase 3: Minimal Residual Disease (MRD) Over Time		Up to approximately 5 years
Phase 3: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs)	Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest.	Up to approximately 5 years
Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse by Flow Cytometry for Bone Marrow		Up to approximately 5 years
Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse Identified by Immunohistochemistry or Flow Cytometry for Cerebrospinal Fluid		Up to end of safety follow up (approximately 44 months)
Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse for Extramedullary Sites other than Cerebrospinal Fluid		Up to end of safety follow up (approximately 44 months)
Phase 3: Rate of Lineage Switch to Acute Myeloid Leukemia (AML)		Up to end of safety follow up (approximately 44 months)
Phase 3: Localization of Relapse by Clinical Assessment		Up to end of safety follow up (approximately 44 months)
Phase 3: Mortality Rate in Participants who Experience Complete Remission (CR)		Up to approximately 5 years
Phase 3: Number of Participants who have Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) in Participants who Experience Continuous First Complete Remission (CR)		Up to approximately 5 years
Phase 3: Mortality Rate in Participants who Experience Complete Remission (CR) after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)		Up to approximately 5 years
Phase 3: Relapse Rate Following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)		Up to approximately 5 years
Phase 3: Time to Deterioration using the Fatigue Score	Fatigue score will be measured by PROMIS Fatigue-Short Form 7a.	Up to approximately 5 years
Phase 3: Time to Improvements using the Fatigue Score	Fatigue score will be measured by PROMIS Fatigue-Short Form 7a.	Up to approximately 5 years
Phase 3: Time to Deterioration using the Pain Score	Pain score will be measured by BPI-SF; Item 3: pain at its worst in the last 24 hours.	Up to approximately 5 years
Phase 3: Time to Improvements using the Pain Score	Pain score will be measured by BPI-SF; Item 3: pain at its worst in the last 24 hours.	Up to approximately 5 years
Phase 3: Change from Baseline in Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	EORTC QLQ-C30 will include global health status, physical functioning, emotional functioning, cognitive functioning, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QLQ-C30.	Baseline to end of study (up to approximately 5 years)
Phase 3: Time to Deterioration for Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QCQ-C30.	Up to approximately 5 years
Phase 3: Time to Improvements for Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QCQ-C30.	Up to approximately 5 years
Safety run-in: Minimal Residual Disease (MRD) Relapse Free Survival (RFS)	MRD RFS: In participants who achieve CR with MRD response, the time from first achievement of this response until date of of the first relapse including molecular relapse, hematological relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. (Molecular relapse will be defined 2 ways: MRD>= 10^-3 and MRD>=10^-4. Participants without an event will be censored at their last evaluable disease assessment date.	Up to approximately 5 years
Phase 3: Minimal Residual Disease (MRD) Relapse Free Survival (RFS)	In participants who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD>= 10^-3 and MRD>= 10^-4. Participants without an event will be censored at their last evaluable disease assessment date	Up to approximately 5 years
Steady State Concentration of Blinatumomab		Up to approximately Day 36
Clearance of Blinatumomab		Up to approximately Day 36

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Estimated): September 7, 2029
• Study Completion (Estimated): May 12, 2031

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Blinatumomab; Newly Diagnosed Philadelphia (Ph)-negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL); Low-intensity Chemotherapy; GMALL HyperCVAD
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; blinatumomab
• Other Study ID Numbers: 20190360; 2023-503640-14 (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