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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
NCT04994717 · Amgen
In plain English
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Official title
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)
About this 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.
Eligibility criteria
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 design
Enrollment target: 304 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2021-11-02
Estimated completion: 2031-07-01
Last updated: 2026-04-16
Interventions
Drug: BlinatumomabDrug: Low-intensity chemotherapy regimenDrug: SOC chemotherapy regimen
Primary outcomes
- • Safety run-in: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) (Up to approximately 5 years)
- • Phase 3: Event-free Survival (EFS) (Up to approximately 5 years)
- • Phase 3: Overall Survival (OS) (Up to approximately 5 years)
Sponsor
Amgen · industry
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (192)
City of Hope National Medical CenterRecruiting
Duarte, California, United States
University of California IrvineRecruiting
Orange, California, United States
University of California San FranciscoRecruiting
San Francisco, California, United States
Adventist Health System/Sunbelt, Inc d/b/a AdventHealth OrlandoTerminated
Orlando, Florida, United States
Cleveland Clinic FoundationTerminated
Cleveland, Ohio, United States
Saint Francis Hospital, IncCompleted
Greenville, South Carolina, United States
University of Texas MD Anderson Cancer CenterCompleted
Houston, Texas, United States
Canberra HospitalRecruiting
Garran, Australian Capital Territory, Australia
Royal Prince Alfred HospitalRecruiting
Camperdown, New South Wales, Australia
Liverpool HospitalRecruiting
Liverpool, New South Wales, Australia
Royal North Shore HospitalRecruiting
St Leonards, New South Wales, Australia
Westmead HospitalTerminated
Westmead, New South Wales, Australia
Royal Brisbane and Womens HospitalRecruiting
Herston, Queensland, Australia
Princess Alexandra HospitalRecruiting
Woolloongabba, Queensland, Australia
Royal Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
Monash Medical CentreCompleted
Clayton, Victoria, Australia
Austin Health, Austin HospitalRecruiting
Heidelberg, Victoria, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
The Alfred HospitalRecruiting
Melbourne, Victoria, Australia
Fiona Stanley HospitalRecruiting
Murdoch, Western Australia, Australia
Medizinische Universitaet GrazRecruiting
Graz, Austria
Medizinische Universitaet InnsbruckCompleted
Innsbruck, Austria
Ordensklinikum Linz ElisabethinenCompleted
Linz, Austria
Hanusch KrankenhausCompleted
Vienna, Austria
Institut Jules BordetRecruiting
Anderlecht, Belgium
AZ Sint-Jan Brugge-Oostende AVRecruiting
Bruges, Belgium
Universite Catholique de Louvain Cliniques Universitaires Saint LucTerminated
Brussels, Belgium
Universitair Ziekenhuis AntwerpenRecruiting
Edegem, Belgium
Universitair Ziekenhuis GentRecruiting
Ghent, Belgium
Jessa Ziekenhuis - Campus Virga JesseRecruiting
Hasselt, Belgium
Centre Hospitalier Universitaire de Liege - Sart TilmanRecruiting
Liège, Belgium
AZ Delta Campus RumbekeRecruiting
Roeselare, Belgium
Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site GodinneRecruiting
Yvoir, Belgium
Igesd Instituto de Gestao Estrategica da Saude do Distrito FederalRecruiting
Brasília, Federal District, Brazil
Hospital das Clinicas da Universidade Federal de GoiasRecruiting
Goiânia, Goiás, Brazil
Hospital 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
Hospital de Base de Sao Jose do Rio PretoRecruiting
São Jose Do Rio Preto, São Paulo, Brazil
HemorioRecruiting
Rio de Janeiro, Brazil
Instituto Cancer Sao Paulo IcespRecruiting
São Paulo, Brazil
University Multiprofile Hospital for Active Treatment Sveti Georgi EADRecruiting
Plovdiv, Bulgaria
Specialized Hospital for Active Treatment of Hematology Diseases EADTerminated
Sofia, Bulgaria
Arthur J E Child Comprehensive Cancer CentreRecruiting
Calgary, Alberta, Canada
Vancouver General Hospital, Gordon and Leslie Diamond Health Care CentreRecruiting
Vancouver, British Columbia, Canada
Cancer Care ManitobaRecruiting
Winnipeg, Manitoba, Canada
Queen Elizabeth II, Health Sciences CentreRecruiting
Halifax, Nova Scotia, Canada
Hamilton Health Sciences - Juravinski Hospital and Cancer CentreRecruiting
Hamilton, Ontario, Canada
The Ottawa Hospital Cancer CentreRecruiting
Ottawa, Ontario, Canada
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
CEMTL Hopital Maisonneuve RosemontRecruiting
Montreal, Quebec, Canada
Fundacion Arturo Lopez PerezRecruiting
Santiago, Chile
InmunocelRecruiting
Santiago, Chile
Clinica Alemana de SantiagoRecruiting
Santiago, Chile
Fakultni nemocnice BrnoRecruiting
Brno, Czechia
Fakultni nemocnice Hradec KraloveRecruiting
Hradec Králové, Czechia
Ustav hematologie a krevni transfuzeRecruiting
Prague, Czechia
Aalborg UniversitetshospitalRecruiting
Aalborg, Denmark
Aarhus UniversitetshospitalRecruiting
Aarhus N, Denmark
RigshospitaletRecruiting
København Ø, Denmark
Odense UniversitetshospitalRecruiting
Odense, Denmark
North Estonia Medical CentreTerminated
Tallinn, Estonia
Tartu University HospitalTerminated
Tartu, Estonia
Helsinki University HospitalRecruiting
Helsinki, Finland
Turku University HospitalRecruiting
Turku, Finland
Hopital Henri MondorRecruiting
Créteil, France
Centre Hospitalier Universitaire de Dijon - Hopital du BocageRecruiting
Dijon, France
Centre Hospitalier de Versailles - Hopital Andre MignotRecruiting
Le Chesnay, France
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude HuriezRecruiting
Lille, France
Institut Paoli CalmettesRecruiting
Marseille, France
Centre Hospitalier Universitaire de Nantes - Hopital Hotel DieuRecruiting
Nantes, France
Centre Hospitalier Universitaire Archet 2Recruiting
Nice, France
Hopital Saint LouisRecruiting
Paris, France
Hopital Saint AntoineRecruiting
Paris, France
Centre Hospitalier Universitaire de Bordeaux - Hopital Haut LevequeRecruiting
Pessac, France
Hopital Lyon SudRecruiting
Pierre-Bénite, France
Centre Hospitalier Universitaire de RennesRecruiting
Rennes, France
Institut Universitaire du Cancer Toulouse OncopoleRecruiting
Toulouse, France
Centre Hospitalier Universitaire de Nancy - Hopital de BraboisRecruiting
Vandœuvre-lès-Nancy, France
Universitaetsklinikum AugsburgCompleted
Augsburg, Germany
Charite - Universitaetsmedizin Berlin, Campus Benjamin FranklinCompleted
Berlin, Germany
Universitaetsklinikum DresdenCompleted
Dresden, Germany
Universitaetsklinikum DuesseldorfCompleted
Düsseldorf, Germany
Universitaetsklinikum HeidelbergCompleted
Heidelberg, Germany
Universitaetsklinikum JenaCompleted
Jena, Germany
Universitaetsklinikum Schleswig-Holstein - KielCompleted
Kiel, Germany
Klinikum der LMU MuenchenCompleted
München, Germany
Evangelismos HospitalRecruiting
Athens, Greece
Laiko General Hospital of AthensRecruiting
Athens, Greece
Attiko General University HospitalRecruiting
Athens, Greece
University Hospital of HeraklionRecruiting
Heraklion, Greece
University Hospital of IoanninaRecruiting
Ioannina, Greece
University Hospital of LarissaRecruiting
Larissa, Greece
University Hospital of PatrasRecruiting
Pátrai, Greece
General Hospital of Thessaloniki Georgios PapanikolaouRecruiting
Thessaloniki, Greece
Queen Mary Hospital, The University of Hong KongRecruiting
Hong Kong, Hong Kong
Princess Margaret HospitalRecruiting
Kowloon, Hong Kong
Tuen Mun HospitalRecruiting
New Territories, Hong Kong
Semmelweis EgyetemRecruiting
Budapest, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai IntezetRecruiting
Budapest, Hungary
Debreceni Egyetem Klinikai KozpontRecruiting
Debrecen, Hungary
Heves Varmegyei Markhot Ferenc Oktatokorhaz es RendelointezetRecruiting
Eger, Hungary
Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz Nyiregyhazi Josa Andras TagkorhazRecruiting
Nyíregyháza, Hungary
Rambam Medical CenterRecruiting
Haifa, Israel
Shaare Zedek Medical CenterRecruiting
Jerusalem, Israel
Rabin Medical Center - Beilinson HospitalRecruiting
Petah Tikva, Israel
Azienda Ospedaliera Universitaria Consorziale Policlinico di BariTerminated
Bari, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni xxiiiRecruiting
Bergamo, Italy
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant OrsolaRecruiting
Bologna, Italy
Ospedale Policlinico San Martino IRCCSRecruiting
Genova, Italy
Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo IITerminated
Lecce, Italy
Azienda Unità Locale Socio Sanitaria 3 Ospedale Dell AngeloRecruiting
Mestre (VE), Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore PoliclinicoRecruiting
Milan, Italy
Azienda Ospedaliera di Rilievo Nazionale Antonio CardarelliRecruiting
Naples, Italy
Azienda Ospedaliera di Perugia Ospedale Santa Maria della MisericordiaRecruiting
Perugia, Italy
Azienda Unita Sanitaria Locale Pescara Ospedale Civile Santo SpiritoRecruiting
Pescara, Italy
Azienda Ospedaliera Policlinico Umberto IRecruiting
Roma, Italy
Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di TorinoRecruiting
Torino, Italy
Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo RomaTerminated
Verona, Italy
Nagoya University HospitalRecruiting
Nagoya, Aichi-ken, Japan
Akita University HospitalRecruiting
Akita, Akita, Japan
Tesshokai Kameda General HospitalRecruiting
Kamogawa-shi, Chiba, Japan
University of Fukui HospitalRecruiting
Yoshida-gun, Fukui, Japan
Kyushu University HospitalRecruiting
Fukuoka, Fukuoka, Japan
Kurume University HospitalRecruiting
Kurume-shi, Fukuoka, Japan
Fukushima Medical University HospitalRecruiting
Fukushima, Fukushima, Japan
Gunma Saiseikai Maebashi HospitalRecruiting
Maebashi, Gunma, Japan
Sapporo Hokuyu HospitalRecruiting
Sapporo, Hokkaido, Japan
Kobe City Medical Center General HospitalRecruiting
Kobe, Hyōgo, Japan
Kanazawa University HospitalRecruiting
Kanazawa, Ishikawa-ken, Japan
Tokai University HospitalRecruiting
Isehara-shi, Kanagawa, Japan
Yokohama City University Medical CenterRecruiting
Yokohama, Kanagawa, Japan
Kyoto University HospitalRecruiting
Kyoto, Kyoto, Japan
Tohoku University HospitalRecruiting
Sendai, Miyagi, Japan
Nagasaki University HospitalRecruiting
Nagasaki, Nagasaki, Japan
National Hospital Organization Okayama Medical CenterRecruiting
Okayama, Okayama-ken, Japan
Osaka Metropolitan University HospitalRecruiting
Osaka, Osaka, Japan
Kindai University HospitalRecruiting
Sakai-shi, Osaka, Japan
Jichi Medical University HospitalRecruiting
Shimotsuke-shi, Tochigi, Japan
Tokyo Metropolitan Komagome HospitalRecruiting
Bunkyo-ku, Tokyo, Japan
Nihon University Itabashi HospitalRecruiting
Itabashi-ku, Tokyo, Japan
Yamagata University HospitalRecruiting
Yamagata, Yamagata, Japan
Boca Clinical Trials Mexico SCTerminated
Mexico City, Mexico City, Mexico
Centro Oncologico InternacionalRecruiting
Mexico City, Mexico City, Mexico
Hospital Universitario Dr Jose Eleuterio GonzalezRecruiting
Monterrey, Nuevo León, Mexico
Hematologica Alta EspecialidadRecruiting
Huixquilucan, Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRecruiting
Mexico City, Mexico
Universitair Medisch Centrum GroningenActive Not Recruiting
Groningen, Netherlands
Unidade Local de Saude de Coimbra, EPERecruiting
Coimbra, Portugal
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPERecruiting
Lisbon, Portugal
Unidade Local de Saude de Sao Jose, EPE - Hospital de Santo Antonio dos CapuchosRecruiting
Lisbon, Portugal
Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa MariaRecruiting
Lisbon, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPERecruiting
Porto, Portugal
Institutul Clinic FundeniRecruiting
Bucharest, Romania
Spitalul Universitar de Urgenta BucurestiRecruiting
Bucharest, Romania
Institutul Oncologic Prof Dr Ion ChiricutaRecruiting
Cluj-Napoca, Romania
Spitalul Clinic Municipal Filantropia CraiovaRecruiting
Craiova, Romania
Institutul Regional de Oncologie IasiRecruiting
Iași, Romania
Spitalul Clinic Judetean de Urgenta SibiuRecruiting
Sibiu, Romania
Narodny onkologicky ustavRecruiting
Bratislava, Slovakia
Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a MetodaRecruiting
Bratislava, Slovakia
Dong-A University HospitalRecruiting
Busan, South Korea
Pusan National University HospitalRecruiting
Busan, South Korea
Chungnam National University HospitalRecruiting
Daejeon, South Korea
Chonnam National University Hwasun HospitalRecruiting
Hwasun, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Severance Hospital Yonsei University Health SystemRecruiting
Seoul, South Korea
The Catholic University of Korea Seoul St Marys HospitalRecruiting
Seoul, South Korea
Hospital Universitario Reina SofiaRecruiting
Córdoba, Andalusia, Spain
Hospital Universitario Virgen del RocioTerminated
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 Universitari Vall d HebronRecruiting
Barcelona, Catalonia, Spain
Institut Catala d Oncologia Hospitalet Hospital Duran i ReynalsRecruiting
L'Hospitalet de Llobregat, Catalonia, Spain
Hospital Universitari i Politecnic La FeRecruiting
Valencia, Valencia, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Sahlgrenska UniversitetssjukhusetRecruiting
Gothenburg, Sweden
Inselspital BernActive Not Recruiting
Bern, Switzerland
China Medical University HospitalRecruiting
Taichung, Taiwan
Taichung Veterans General HospitalRecruiting
Taichung, Taiwan
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Linkou Chang Gung Memorial Hospital of Chang Gung Medical FoundationRecruiting
Taoyuan District, Taiwan
Hacettepe Universitesi Tip Fakultesi HastanesiRecruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Sehir HastanesiRecruiting
Ankara, Turkey (Türkiye)
Memorial Antalya HastanesiRecruiting
Antalya, Turkey (Türkiye)
Bagcilar Medipol Mega Universite HastanesiRecruiting
Istanbul, Turkey (Türkiye)
Dokuz Eylul Universitesi Tip Fakultesi HastanesiRecruiting
Izmir, Turkey (Türkiye)
Ondokuz Mayis Universitesi Tip Fakultesi HastanesiRecruiting
Samsun, Turkey (Türkiye)
University College LondonCompleted
London, United Kingdom
Kings College HospitalRecruiting
London, United Kingdom