BLINATUMOMAB for Acute lymphoblastic leukaemia (B-cell precursor, Philadelphia-negative)

Inclusion criteria

• {"criterion_text":"- Subject has provided informed consent prior to initiation of any study specific activities/procedures OR Where permitted by local law, subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.\n- 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 aminotransferase (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 subjects in both the experimental and the SOC arm. The subject history needs to be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.\n- Subjects with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) per WHO criteria\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score allowed if due to underlying leukemia.\n- All subjects must have adequate organ function as defined below: - renal: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 50 mL/min/1.73 m2 - liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert’s Disease or if liver involvement with leukemia); exception for subjects 40 to < 55 years of age if comorbidity is per inclusion 102: 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

• {"criterion_text":"- Active CNS leukemia (i.e, CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening\n- 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.\n- History or presence of clinically relevant CNS pathology or eventsuch as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's diease, cerebellar disease, organic brain syndrome, or psychiatric conditions that preclude the use of high dose of corticosteroids. Consult with medical monitor as needed.\n- Current autoimmune disease or history of autoimmune disease with potential CNS involvement\n- Known infection with human immunodeficiency virus (HIV)\n- Known infection with chronic or active 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.\n- Subject with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection.\n- Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or pre-phase chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.\n- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded."}

Primary endpoints

• {"endpoint_text":"- SRI: Treatment-emergent adverse events, treatment-related adverse events, and adverse events of interest","definition_or_measurement_approach":""}
• {"endpoint_text":"- Ph3: EFS: time from randomization until treatment failure, relapse, or death from any cause, whichever is earlier. Subjects without an event will be censored at their last evaluable disease assessment date.","definition_or_measurement_approach":"Time from randomization until treatment failure, relapse, or death from any cause; subjects without an event are censored at their last evaluable disease assessment date."}
• {"endpoint_text":"- Ph3: OS: time from randomization until death due to any cause. Subjects alive will be censored at the date last known to be alive.","definition_or_measurement_approach":"Time from randomization until death from any cause; subjects alive are censored at last known alive date."}

Methods

• HCP referral (Dr-to-Dr referral letters and HCP study fact sheets) – materials provided to healthcare professionals to identify eligible patients
• Patient-facing recruitment materials (Patient Journey leaflets, patient diaries) distributed to potential participants to explain study arms and procedures
• GP/Primary care letters to inform local physicians about participant enrollment and study details
• Provisioning of ePRO/eCOA tablets and electronic patient-reported outcome collection (ePRO) for patient-reported endpoints
• Home healthcare support and IP-to-home processes described (home healthcare visits for IV bag changes; site-to-patient shipment procedures) to facilitate participation

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Excelya Greece CRO Single Member S.A.

Responsibilities

Submission activities; local submission support (as listed in sponsor third parties)

Name

Fortrea Inc.

Responsibilities

Infusion pump training and support; Home Healthcare visits for IV bag change at subject’s home

Name

Altasciences Compagnie Inc.

Responsibilities

Operational support (as listed under sponsor third parties)

Third parties

• {"country":"Germany","full_name":"Amgen Research (Munich) GmbH","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Excelya Greece CRO Single Member S.A.","duties_or_roles":"Submission activities; sponsor duties codes: 1 and 15 (Submission activities)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Amgen Limited","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Infusion pump training and support; Home Healthcare visits for IV bag change at subject’s home (Submission activities code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsor duties code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central Lab providing Laboratory Supplies, Lab Manuals and sample management. No sample analysis is completed","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"Provisioning of ePRO tablets and collection of ePRO data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Amgen Inc. (US operational address)","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eurofins Panlabs Inc.","duties_or_roles":"sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsor duties code: 4","organisation_type":"Non-Pharmaceutical company"}