Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma (ZUMA-22)

A Phase 3 Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Follicular Lymphoma

The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Follicular Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Prednisone; Biological: Axicabtagene Ciloleucel; Drug: Lenalidomide; Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Bendamustine

Detailed Description

Five years after the last study participant is randomized, participants who have received axicabtagene ciloleucel will transition to a separate Long-term Follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Hopital Henri Mondor
  • Dijon, France, 21079
    • CHU de DIJON
  • Lille, France, 59037
    • Hôpital Claude Huriez-CHU de Lille
  • Marseille, France, 13273
    • Institut Paoli-Calmettes
  • Montpellier, France, 34295
    • Hopital Saint Eloi
  • Paris, France, 75013
    • Hôpital Pitié-Salpêtrière
  • Pessac, France, 33604
    • CHU Bordeaux - Hospital Haut-Leveque - Centre Francois Magendie
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • Chu de Poitiers
  • Rennes, France, 35033
    • Hopital Pontchaillou - CHU Rennes
  • Rouen, France, 76038
    • Centre Henri Becquerel
• Germany
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen
  • Würzburg, Germany, 97080
    • Universitatsklinikum Koln Klinik I fur Innere Medizin
• Italy
  • Bergamo, Italy, 24128
    • Asst Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Azienda Ospedallero-Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20100
    • Fondazione IRCCS - Istituto Nazionale Tumori
  • Reggio Emilia, Italy, 42123
    • Arcispedale Santa Maria Nuova
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas-IRCCS
• Japan
  • Hyōgo, Japan, 663-8501
    • Hyogo Medical University Hospital
  • Kyoto, Japan, 602-8566,
    • University Hospital Kyoto Prefectural University of Medicine
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08908
    • Instituto Catalan de Oncologia - Hospital Duran i Reynolds (ICO L'Hospitalet)
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospital Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 2QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, NW2 2QG
    • University College London Hospitals NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • The University Hospital Southampton NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Stanford, California, United States, 94305
      • Stanford Health Care
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute Hematology - Charlotte
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
    • Nashville, Tennessee, United States, 37203
      • TriStar Centennial Medical Center - Cell Processing
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically-confirmed follicular lymphoma (FL) (Grade 1, 2, or 3a)
• Relapsed/refractory (R/r) disease after first-line chemoimmunotherapy and high-risk disease with relapse or progression within 24 months of the initial course of chemoimmunotherapy (ie, POD24), Or r/r disease after ≥ 2 prior systemic lines of therapy
• Clinical indication for treatment.
• At least 1 measurable lesion per the Lugano Classification {Cheson 2014}
• Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

• Presence of large B cell lymphoma or transformed FL
• Small lymphocytic lymphoma
• Lymphoplasmacytic lymphoma
• Full-thickness involvement of the gastric wall by lymphoma
• FL Grade 3b
• Prior CD19-targeted therapy
• Prior CAR therapy or other genetically modified T-cell therapy
• Uncontrolled fungal, bacterial, viral, or other infection
• Active Infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus
• History or presence of a clincially significant central nervous system (CNS) disorder.
• History of autoimmune disease
• Known history or CNS lymphoma involvement
• Cardiac lymphoma involvement
• History of clinically significant cardiac disease 6 months before randomization
• Neuropathy greater than grade 2
• Females who are pregnant or breastfeeding
• Individuals of both genders who are not willing to practice birth control
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, pleural/peritoneal/pericardial catheter, or Ommaya reservoirs). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care Therapy; Participants will receive the investigator's choice of one of the following therapies/dosing schedules: Rituximab plus lenalidomide (R^2) for 12 cycles (28-day cycle)Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m^2 on Day 1, Day 8, Day 15, and Day 22Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle)rituximab 375 mg/m^2 on Day 1cyclophosphamide 750 mg/m^2 on Day 1doxorubicin 50 mg/m^2 on Day 1vincristine 1.4 mg/m^2 (maximum 2 mg) on Day 1prednisone 40 mg/m^2 on Day 1 through Day 5; Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle)rituximab 375 mg/m^2 on Day 1bendamustine 90 mg/m^2 on Day 1 and Day 2	Drug: Cyclophosphamide; Administered intravenously; Drug: Prednisone; Administered orally; Drug: Lenalidomide; Administered orally; Drug: Rituximab; Administered intravenously; Drug: Doxorubicin; Administered intravenously; Drug: Vincristine; Administered intravenously; Drug: Bendamustine; Administered intravenously
Experimental: Axicabtagene Ciloleucel; Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: Axicabtagene Ciloleucel; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells; Other Names: Yescarta®; axi-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification	CR rate is defined as the proportion of participants with best overall response of CR during the study prior to any subsequent off-protocol anti-follicular lymphoma (FL) therapy.	Up to 5 years
Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification	Objective response rate is defined as the proportion of participants with best overall response of either a complete response or a partial response during the study prior to any subsequent off-protocol anti-FL therapy.	Up to 5 years
Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification	DOR is defined as the time from first objective response to disease progression or death from any cause.	Up to 5 years
Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification	Duration of CR is defined as the time from first CR to disease progression or death from any cause.	Up to 5 years
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to 5 years
Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification	EFS is defined as the time from randomization to the earliest date of disease progression, the initiation of subsequent off-protocol anti-FL therapy, or death from any cause.	Up to 5 years
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		Randomization up to 5 years plus 30 days
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values		Randomization up to 5 years plus 30 days
Change From Baseline in the Global Health Status Quality of Life Scale of the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30)	The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30	The EORTC-QLQ-C30) is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Change From Baseline in the Global Health Status Quality of Life Scale of the Low Grade Non-Hodgkin Lymphoma-20 (NHL-LG20)	The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Change From Baseline in the Physical Functioning Domain of the NHL-LG20	The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L)	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.	Baseline, up to 5 years
Changes From Baseline in the Visual Analog Scale (VAS) Scores	The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). Higher scores indicate better health.	Baseline, up to 5 years
Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start of subsequent off-protocol anti-lymphoma therapy or death from any cause.	Up to 5 years
Percentage of Participants with Replication-competent Retrovirus in Blood Over time		Up to 5 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: May 9, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 12, 2022

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Acids, Acyclic; Carboxylic Acids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Piperidines; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Butyrates; Antibodies, Monoclonal, Murine-Derived; Daunorubicin; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bendamustine Hydrochloride; Rituximab; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; fludarabine; axicabtagene ciloleucel
• Other Study ID Numbers: KT-US-473-0133; 2021-003260-28 (EudraCT Number: European Medicines Agency); 2024-511594-30 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No