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
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
Sex
ALL
Min age
40 Years
Max age
100 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Safety run-in: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) — Up to approximately 5 years Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest.
Phase 3: Event-free Survival (EFS) — Up to approximately 5 years 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.
Phase 3: Overall Survival (OS) — Up to approximately 5 years OS is defined as time from randomization (enrollment) until death due to any cause.
Trial sites (192)
Facility
City
Region
Status
City of Hope National Medical Center
Duarte
California
University of California Irvine
Orange
California
University of California San Francisco
San Francisco
California
Adventist Health System/Sunbelt, Inc d/b/a AdventHealth Orlando
Orlando
Florida
Cleveland Clinic Foundation
Cleveland
Ohio
Saint Francis Hospital, Inc
Greenville
South Carolina
University of Texas MD Anderson Cancer Center
Houston
Texas
Canberra Hospital
Garran
Australian Capital Territory
Royal Prince Alfred Hospital
Camperdown
New South Wales
Liverpool Hospital
Liverpool
New South Wales
Royal North Shore Hospital
St Leonards
New South Wales
Westmead Hospital
Westmead
New South Wales
Royal Brisbane and Womens Hospital
Herston
Queensland
Princess Alexandra Hospital
Woolloongabba
Queensland
Royal Adelaide Hospital
Adelaide
South Australia
Monash Medical Centre
Clayton
Victoria
Austin Health, Austin Hospital
Heidelberg
Victoria
Peter MacCallum Cancer Centre
Melbourne
Victoria
The Alfred Hospital
Melbourne
Victoria
Fiona Stanley Hospital
Murdoch
Western Australia
Medizinische Universitaet Graz
Graz
Austria
Medizinische Universitaet Innsbruck
Innsbruck
Austria
Ordensklinikum Linz Elisabethinen
Linz
Austria
Hanusch Krankenhaus
Vienna
Austria
Institut Jules Bordet
Anderlecht
Belgium
AZ Sint-Jan Brugge-Oostende AV
Bruges
Belgium
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels
Belgium
Universitair Ziekenhuis Antwerpen
Edegem
Belgium
Universitair Ziekenhuis Gent
Ghent
Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt
Belgium
Centre Hospitalier Universitaire de Liege - Sart Tilman
Liège
Belgium
AZ Delta Campus Rumbeke
Roeselare
Belgium
Centre Hospitalier Universitaire-Universite Catholique de Louvain Namur-Site Godinne
Yvoir
Belgium
Igesd Instituto de Gestao Estrategica da Saude do Distrito Federal
Brasília
Federal District
Hospital das Clinicas da Universidade Federal de Goias
Goiânia
Goiás
Hospital de Clinicas de Porto Alegre
Porto Alegre
Rio Grande do Sul
Fundacao Amaral Carvalho
Jaú
São Paulo
Hosp Clin Fac Med Ribeirao Preto Usp
Ribeirão Preto
São Paulo
Hospital de Base de Sao Jose do Rio Preto
São Jose Do Rio Preto
São Paulo
Hemorio
Rio de Janeiro
Brazil
+ 152 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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