Active, not recruiting
Phase 3
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
Condition(s) studied
Newly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)
Investigational drug(s) / intervention(s)
BlinatumomabLow-intensity chemotherapy regimenSOC chemotherapy regimen
Blinatumomab: Continuous intravenous (cIV) infusion
Low-intensity chemotherapy regimen: Intravenous (IV), oral (PO), subcutaneous (SC), or intrathecal (IT) administration.
SOC chemotherapy regimen: Intravenous (IV), oral (PO), subcutaneous (SC), or intrathecal (IT) administration.
Study summary
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
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.
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