20190360 (Golden Gate Study)

Newly diagnosed Ph-negative B-cell precursor ALL. Adults aged >= 55 or aged 40–54 with specific comorbidities. ECOG performance status <= 2

101 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. 102 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: a. history of grades 3 and 4 pancreatitis. b. diabetes mellitus with end-organ damage. c. 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 times upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy). d. body mass index (BMI) >= 40 combined with relevant comorbidities such as metabolic syndrome. e. 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. 103 Subjects with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) per WHO criteria. 104 Eastern Cooperative Oncology Group (ECOG) performance status <= 2, higher ECOG score allowed if due to underlying leukemia. 106 All subjects must have adequate organ function as defined below: a. renal: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation >= 50 mL/min/1.73 m². b. liver function: total bilirubin <= 2 times 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 times ULN (liver cirrhosis must be confirmed by biopsy). c. cardiac: left ventricular ejection fraction (LVEF) >= 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months).

Active CNS leukemia not resolved during screening. Prior chemotherapy for the current ALL diagnosis. Relevant history of other malignancies or CNS pathology.

201 Active CNS leukemia (ie, CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening. 202 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 $\ge 3$ 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. 226 History or presence of 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. 204 Current autoimmune disease or history of autoimmune disease with potential CNS involvement. 219 Known infection with human immunodeficiency virus (HIV). 220 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). 221 Subject with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection. 207 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. 208 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). 209 Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 12 months after the last dose of protocol-required therapy. 210 Female subjects who are breastfeeding or who plan to breastfeed while on study through 12 months after the last dose of protocol-required therapy. 216 Subject has known sensitivity to any of the products or components to be administered during dosing. 218 History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.