Study Evaluating the Efficacy of KITE-753 Versus Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma After First-Line Therapy

NCT07479797 | Not Yet Recruiting Phase 3 FDA Drug

• 2 other identifiers: KT-US-740-06032025-524403-80-00
• Study Type: interventional
• Target: 550
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical study is to compare the study drug KITE-753 versus axicabtagene ciloleucel (axi-cel) in adult participants with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) after one prior line of therapy. The primary objective of this study is to evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel.

Conditions

Relapsed or Refractory Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants in Complete Response (CR) at Month 6

  Participants who would be in CR at Month 6 postinfusion of KITE-753 or axi-cel and prior to subsequent anti-lymphoma therapy. This will be assessed by the Lugano Classification by the blinded central assessment.

  Month 6

• Event-free survival (EFS)

  EFS is defined as the time from randomization to the earliest occurrence of the following EFS events: a) Death due to any cause, b) Disease progression/relapse per blinded central assessment, and c) Initiation of any non-protocol specified subsequent anti-lymphoma therapy for the treatment of residual disease (including stable disease and partial response as per International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma).

  Up to 36 months

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

• Duration of Response (DOR)

  Up to 36 months

• Duration of Complete Response (DOCR)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (2)

Lymphodepleting Chemotherapy: KITE-753

EXPERIMENTAL

Participants with r/r LBCL will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine and cyclophosphamide. * A single infusion at a target dose of anti-cluster of differentiation 19 (CD19)/CD20 chimeric antigen receptor (CAR) T cells/kg of KITE-753.

Drug: KITE-753; Drug: Fludarabine; Drug: Cyclophosphamide

Lymphodepleting Chemotherapy: Axicabtagene Ciloleucel (axi-cel)

EXPERIMENTAL

Participants with r/r LBCL will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine and cyclophosphamide. * A single infusion at a target dose of anti-CD19/CD20 CAR T cells/kg of axi-cel.

Drug: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Axicabtagene Ciloleucel DRUG

A single infusion of CAR-transduced autologous T cells administered as intravenous infusion.

Lymphodepleting Chemotherapy: Axicabtagene Ciloleucel (axi-cel)

Cyclophosphamide DRUG

Administered intravenously

Lymphodepleting Chemotherapy: Axicabtagene Ciloleucel (axi-cel); Lymphodepleting Chemotherapy: KITE-753

KITE-753 DRUG

A single infusion of CAR-transduced autologous T cells administered as intravenous infusion.

Lymphodepleting Chemotherapy: KITE-753

Fludarabine DRUG

Administered intravenously

Lymphodepleting Chemotherapy: Axicabtagene Ciloleucel (axi-cel); Lymphodepleting Chemotherapy: KITE-753

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with any of the following large B-cell lymphomas, as determined by the investigator, are eligible for the study as defined below:
• World Health Organization (WHO):
• Individuals with chemorefractory disease to first-line therapy (primary refractory disease) that satisfies any of the following criteria:
• Progressive disease (PD) and/or Deauville score of 5 (irrespective of the response designation) as the best response during the first-line treatment or as the end of treatment response following first-line therapy.
• Stable disease (SD) after at least 4 cycles of first-line therapy (eg, 4 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)).
• PR as best response after at least 6 cycles of first-line therapy (eg, 6 cycles of R-CHOP).
• Note: A biopsy is recommended to confirm residual disease.
• Individuals with relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapsed ≤ 12 months of completion of first-line therapy.
• Note: If the relapse is confirmed by imaging per International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma within 12 months, the confirmatory biopsy must be performed within 90 days of the 12-month cutoff.
• Prior therapy must have included an anti-CD20 antibody (including CD20-targeting T-cell engager antibodies) and an anthracycline-containing chemotherapy regimen.
• For individuals with transformed indolent NHL, therapies given for non-transformed disease do not count as a line of therapy for the transformed disease.
• Individuals who have had no additional systemic therapy or holding therapy (except for steroids and/or local radiation) following first-line therapy and prior to leukapheresis are eligible.
• At least 1 measurable lesion according to the IWG Lugano Response Criteria. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. A measurable lesion is defined as \>1.5 cm longest transverse diameter (LDi) for lymph node and \> 1.0 cm LDi for extranodal lesion. Splenomegaly or hepatomegaly alone in the absence of a measurable lesion is not considered to be measurable disease.
• The following washout period must be satisfied:
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the individual is randomized.

You may not qualify if:

• 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 care 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.
• History of a severe, immediate hypersensitivity reaction attributed to aminoglycosides
• 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).
• 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.
• 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 enrollment. 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.

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Recurrence

Interventions

axicabtagene ciloleucel; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Central Study Contacts

Medical Information

CONTACT

844-454-5483(1-844-454-KITE); medinfo@kitepharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: March 18, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share