Inclusion criteria, exclusion criteria and study summary
1) Histologically-confirmed FL (grade 1, 2, or 3a) per local diagnosis. If clinically permissible, a new biopsy is strongly recommended at screening to exclude subjects with transformed disease or those who were initially misdiagnosed. Tumor tissue must be provided for retrospective central pathology review. If an archival specimen is not available, a new biopsy is required prior to randomization. 2) R/r disease as defined as one of the following options: a) At least 1 prior line and high-risk disease, defined as relapse or progression within 24 months of initiation (Cycle 1 Day 1) of the first course of chemoimmunotherapy consisting of an anti-CD20 monoclonal antibody plus either B, CHOP, or CVP (ie, POD24). Progression is measured from the first day of the first cycle of the initial chemoimmunotherapy. The first line of chemoimmunotherapy must have consisted of at least 3 cycles of an anti-CD20 monoclonal antibody plus either B, CHOP, or CVP. The CHOP regimen may have included a prednisone-equivalent dose of another corticosteroid. Frontline anti-CD20 monoclonal antibody monotherapy before an initial line of chemoimmunotherapy is permissible and not considered a line of therapy for purposes of eligibility. For those who received consolidation or maintenance therapy, the timing of progression from chemoimmunotherapy will be counted from the initiation of initial chemoimmunotherapy. OR b) R/r disease after ≥ 2 prior lines of therapy. Involved field/site radiation, maintenance, and consolidation therapies are not considered separate lines of therapy for purposes of eligibility. Single-agent anti-CD20 will not be considered a separate line of therapy for purposes of eligibility. Subjects with stable disease for < 1 year following their last line of therapy are eligible. 3) Clinical indication for treatment, including but not limited to local symptoms due to progressive or bulky disease, systemic B symptoms, compromised organ function due to disease progression, cytopenias due to marrow involvement, or symptomatic extranodal disease. 4) At least 1 measurable lesion per the Lugano Classification {Cheson 2014} on anatomical imaging such as computed tomography (CT) imaging (functional imaging such as positron emission tomography [PET] may not be used to identify a measurable lesion). Previously irradiated lesions are considered measurable only if progression was documented following completion of radiation therapy. 5) No known history or suspicion of central nervous system (CNS) lymphoma involvement. 6) Elapsed time of at least 2 weeks or 5 half-lives, whichever was shorter, since any prior systemic therapy and randomization, except for systemic inhibitory/stimulatory immune checkpoint therapy. Elapsed time of at least 3 half-lives since any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy and randomization (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, and 4-1BB agonists). 7) Toxicities due to prior therapy must have been stable and recovered to Grade 1 or lower (except for clinically nonsignificant toxicities, such as alopecia). 8) Age 18 or older. 9) Eastern Cooperative Performance Status of 0 or 1. 10) Absolute neutrophil count ≥ 1000/μL. 11) Platelet count ≥ 75,000/μL. 12) Absolute lymphocyte count ≥ 100/μL. 13) Adequate renal, hepatic, pulmonary, and cardiac function defined as the following: a) Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min b) Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 upper limit of normal c) Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s Syndrome d) Cardiac ejection fraction ≥ 50% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO). Multiple-gated acquisition (MUGA) scan may be used if an ECHO is not available at the site. e) No clinically significant pleural effusion or ascites f) Baseline oxygen saturation > 92% on room air. 14) Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential). Additional information is in Section 4.5.
1) History of transformed FL or clinical evidence of transformed FL at the time of screening. 2) FL grade 3b. 3) History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease-free and without anticancer therapy for at least 3 years. Subjects with asymptomatic localized low-grade prostate cancer, for which a watch-and-wait approach is SOC, are eligible. 4) Intention for subject to proceed to auto-SCT or allogeneic SCT. 5) History of allogenic SCT. 6) Auto-SCT within 6 weeks of the planned axicabtagene ciloleucel infusion. 7) Prior CD19-targeted therapy. 8) Prior CAR therapy or other genetically modified T-cell therapy. 9) History of severe, immediate hypersensitivity reaction attributed to aminoglycosides. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if the subject is responding to active treatment and after consultation with the Kite medical monitor. 10) Infection with human immunodeficiency virus, hepatitis B virus (HBV; ie, hepatitis B surface antigen [HBsAg] positive), or hepatitis C virus (anti-hepatitis C virus-positive). If there is a positive history of HBV or hepatitis C virus, the viral load must be undetectable per quantitative polymerase chain reaction and/or nucleic acid testing. a) Note: Subjects who are seropositive for HBV (ie, hepatitis B surface [HBs] antibody-positive HBs and/or hepatitis B core antibody-positive) are eligible if they are HBsAgnegative and negative for viral DNA. Subjects who are seropositive because of HBV vaccination are eligible (ie, HBs antibody-positive, hepatitis core antibody-negative, and HBsAg-negative). 11) History or presence of a CNS disorder, such as haemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months before randomization, or seizure disorders requiring active anticonvulsive medication. 12) Detectable cerebral spinal fluid (CSF) malignant cells or brain metastases or a history of CNS lymphoma, primary CNS lymphoma, or spinal epidural involvement. 13) Cardiac atrial or cardiac ventricular lymphoma involvement. 14) History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of randomization. 15) Possible requirement for urgent therapy within 6 weeks of randomization due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome [TLS]). 16) History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome. 17) History of non-line associated, clinically significant deep-vein thrombosis (ie, proximal DVT) or pulmonary embolism requiring therapeutic anticoagulation within the 6 months before randomization. 18) Any medical condition likely to interfere with assessment of safety or efficacy study treatment. 19) History of severe hypersensitivity reaction to any of the agents used in this study. 20) Live vaccine ≤ 6 weeks of randomization. 21) Neuropathy greater than Grade 1 (subjects with neuropathy with Grade 1 neuropathy are eligible). 22) Females who are pregnant or breastfeeding (due to potentially dangerous effects of the preparative chemotherapy or SOC on the foetus or infant). 23) Subjects of both genders who are not willing to practice birth control from the time of consent through 12 months following conditioning chemotherapy administration or 12 months after the completion of axicabtagene ciloleucel or SOC, whichever is longer. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential. Subjects of both genders must also comply with any relevant REMS or aRMMs as part of an RMP. Additional information is in Section 4.5. 24) As per the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation (eg, subjects who are at a risk for a thromboembolic event and are not willing to take venous thromboembolism prophylaxis if R2 is prescribed should be excluded).
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