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 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 AST/ALT > 10 x ULN (liver cirrhosis must be confirmed by biopsy); - BMI >= 40 combined with relevant comorbidities such as metabolic syndrome; - any further combination of documented severe comorbidities judged incompatible with intensive pediatric-based adult-adapted chemotherapy but compatible with this protocol (subject history reviewed by medical monitor during screening). - 103 Newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) per WHO criteria. - 104 ECOG performance status <= 2, higher ECOG score allowed if due to underlying leukemia. - 106 Adequate organ function: - renal: eGFR (MDRD) >= 50 mL/min/1.73 m2; - liver: total bilirubin <= 2 x ULN (unless Gilbert’s Disease or liver involvement with leukemia); exception for age 40 to <55 if inclusion 102 severe liver disease comorbidity applies; - cardiac: LVEF >= 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, MI or stroke within 3 months).

Active CNS leukemia not resolved in screening; recent other malignancy (except specified in-situ/low-risk exceptions); significant CNS/autoimmune disease with CNS risk; HIV or active HBV/HCV; uncontrolled infection; prior chemo for new ALL (except IT/pre-phase); concurrent investigational study; key reproductive/contraceptive exclusions; hypersensitivity; inability to comply.

- 201 Active CNS leukemia (CNS 3 leukemia, confirmed by lumbar puncture) not resolved with intrathecal chemotherapy during screening. - 202 History of other malignancy within the past 3 years, except protocol-defined exceptions (eg, curatively treated and inactive >=3 years with low recurrence risk; adequately treated non-melanoma skin cancer/lentigo maligna; cervical carcinoma in situ; breast ductal carcinoma in situ; prostatic intraepithelial neoplasia without prostate cancer; adequately treated noninvasive urothelial papillary carcinoma/carcinoma in situ). - 226 History/presence of clinically relevant CNS pathology/event (eg, epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome) or psychiatric conditions precluding high-dose corticosteroids. - 204 Current autoimmune disease or history of autoimmune disease with potential CNS involvement. - 219 Known HIV infection. - 220 Known chronic/active HBV or HCV infection (protocol-specified virology conditions apply; PCR-negative status required in specified scenarios). - 221 Symptoms/signs/radiographic/sonographic evidence of acute or uncontrolled chronic infection. - 207 Cancer chemotherapy for this newly diagnosed B-cell ALL before protocol-required therapy, except intrathecal chemotherapy or optional pre-phase (debulking) chemotherapy (spot radiation for chloroma/lytic lesion pain or vertebral stabilization allowed). - 208 Currently receiving another investigational device/drug treatment, or <30 days since ending another investigational device/drug study. - 209 Female of childbearing potential unwilling to use protocol-specified contraception during treatment and 12 months after last protocol-required dose. - 210 Female breastfeeding or planning to breastfeed during treatment and 12 months after last protocol-required dose. - 211 Female planning pregnancy or egg donation during treatment and 12 months after last protocol-required dose. - 212 Female of childbearing potential with positive pregnancy test at screening and/or within 3 days before day 1 chemotherapy. - 223 Male with female partner of childbearing potential unwilling to practice abstinence or contraception during treatment and 6 months after last protocol-required dose. - 224 Male with pregnant partner unwilling to practice abstinence or condom use during treatment and 6 months after last protocol-required dose. - 225 Male unwilling to abstain from sperm donation during treatment and 6 months after last protocol-required dose. - 216 Known sensitivity to any products/components administered during dosing. - 222 Subject likely unavailable for protocol-required visits/procedures or unable to comply with required procedures. - 218 Any other clinically significant disorder/condition/disease that, in investigator/Amgen physician opinion, poses safety risk or interferes with study evaluation/procedures/completion.