The trial is taking place at:

Canberra Hospital | Gastroenterology Department

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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

Amgen

Status and phase

Enrolling

Phase 3

Conditions

Newly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)

Treatments

Drug: Low-intensity chemotherapy regimen

Drug: Blinatumomab

Drug: SOC chemotherapy regimen

Study type

Interventional

Funder types

Industry

Identifiers

NCT04994717

20190360

2023-503640-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

284 estimated patients

Sex

All

Ages

40 to 100 years old

Volunteers

No Healthy Volunteers

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
- 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

284 participants in 3 patient groups

Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Blinatumomab

Drug: Low-intensity chemotherapy regimen

Phase 3: Blinatumomab alternating with low-intensity chemotherapy

Experimental group

Description:

Participants will receive blinatumomab alternating with low-intensity chemotherapy.

Treatment:

Drug: Blinatumomab

Drug: Low-intensity chemotherapy regimen

Phase 3: Standard of care (SOC) chemotherapy

Active Comparator group