Comparing KITE-753 with Axicabtagene Ciloleucel for relapsed or refractory large b-cell lymphoma

Exclusion

• −History of a severe, immediate hypersensitivity reaction attributed to aminoglycosides
• −History of a severe immediate hypersensitivity reaction or contraindication to any of the agents used in the study (including fludarabine and cyclophosphamide).
• −Known history of hepatitis B virus (HBV) (hepatitis B surface (HBs) antigen (HBsAg) positive) infection, or hepatitis C (anti-hepatitis C virus (HCV)) positive) infection. History of a hepatitis B or C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) or nucleic acid testing. Note: Individuals who are seropositive for HBV (ie, HBs and/or hepatitis B core antibody positive) are eligible if they are HBsAg-negative and negative for viral DNA. Individuals who are seropositive because of HBV vaccination are eligible (ie, HBs antibody positive, hepatitis core antibody-negative, and HBsAg-negative). Individuals on prophylactic and suppressive antiviral medications against HBV and/or HCV administered per institutional or clinical practice guidelines are eligible.
• −HIV-positive, unless taking appropriate anti-HIV medications, with an undetectable viral load by qPCR and a CD4 count ≥ 200 cells/μL. Note: HIV-positive individuals in Australia are not permitted regardless of active antiretroviral therapy or undetectable blood viral load.
• −Prior CAR T-cell therapy or other cell-based therapy.
• −History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease-free and without anti-cancer therapy (with the exception of hormonal therapy in the case of breast cancer) for at least 3 years. Individuals with asymptomatic localized low-grade prostate cancer for which a watch-and-wait approach is standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → are eligible.
• −Individuals with the following LBCL fifth edition of WHO criteria subtypes: Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, T-cell/histiocyte-rich LBCL, mediastinal gray zone lymphoma, plasmablastic lymphoma, intravascular LBCL, primary central nervous system (CNS) lymphoma, primary vitreoretinal LBCL, fibrin-associated LBCL, fluid overload-associated LBCL lymphomatoid granulomatosis, high-grade B-cell lymphoma (HGBCL) with 11q aberrations, anaplastic lymphoma kinase-positive LBCL, LBCL with Interferon Regulatory Factor 4 (IRF4) rearrangement, and transformed from Hodgkin's lymphoma (HL). Note: Individuals with primary testicular LBCL are eligible.
• −Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management. Note: Simple urinary tract infections and uncomplicated bacterial or viral upper respiratory tract infections are permitted if the individual is responding to active treatment and satisfies the criteria of being afebrile for 48 hours (ie, temperature \< 38°C).
• −History or presence of the following CNS disorders: hemorrhage, dementia (per CTCAE v5.0 Grade 2 or higher memory impairment), cerebellar disease, 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 6 months before enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →. Individuals with seizure disorders requiring active anticonvulsive medication.
• −Individuals with cardiac atrial or cardiac ventricular lymphoma involvement.
• −Individuals with secondary CNS lymphoma.
• −Individuals with full thickness lymphoma involvement of gastric or intestinal lining. Individuals with concern for gastric or intestinal perforation or known contained perforation.
• −History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active unstable/uncontrolled arrhythmia, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within the 6 months before enrollment.
• −Requirement for urgent therapy within 4 weeks before enrollment due to ongoing or impending oncologic emergency (eg, tumor mass effect)
• −Presence of primary immunodeficiency.
• −History of any medical condition including but not limited to autoimmune disease (eg, Crohn's, rheumatoid arthritis, or systemic lupus) resulting in end organ injury or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 90 days. Note: At least 90 days or 5 half-lives, whichever is shorter, must have elapsed after any prior immunosuppressive or immunomodulating therapy that impacts T-cell function and before leukapheresis.
• −History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome.
• −Any medical condition or residual toxicities from prior therapies per investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → assessment likely to interfere with the assessments of safety or efficacy of the study treatment.
• −Live vaccine ≤ 6 weeks before randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →, during the treatment period, and until immune recovery following the study treatments (refer to Section 12.10 for additional country-specific requirements, as applicable).
• −Individuals of either sex who are not willing to practice highly effective birth controlControl groupThe group a new treatment is measured against.Read more → from the time of informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → through 12 months after the completion of KITE-753 or axi-cel infusion.
• −In the investigator's judgment, the individual is unlikely to complete all study-specific visits or procedures, including follow-upFollow-upContinued check-ins after the treatment part is finished.Read more → visits, or comply with the study requirements for participation.
• −Note: Other protocolProtocolThe detailed plan a study must follow.Read more → defined InclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more →/Exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → may apply.
• −Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of childbearing potential.