A Study of Axicabtagene Ciloleucel in Participants With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

NCT03105336 — Phase 2, Completed, 159 participants, Kite, A Gilead Company

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A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)

Registry	NCT03105336, acronym ZUMA-5
Status	Completed
Phase	Phase 2
Study type	Interventional; non randomized, parallel, masking: none, treatment
Enrollment	159 (Actual)
Sponsor	Kite, A Gilead Company (Industry)
Conditions	Follicular Lymphoma, Marginal Zone Lymphoma, Indolent Non-Hodgkin Lymphoma
Interventions	Axicabtagene ciloleucel, Cyclophosphamide, Fludarabine (Biological, drug)
Dates	start 2017-06-06, primary completion 2024-12-20, completion 2024-12-20, first posted 2017-04-07, last updated 2025-12-23
Locations	19 sites in United States, France

-Summary

The goal of this study is to assess whether axicabtagene ciloleucel improves the clinical outcome in participants with relapsed or refractory indolent non-Hodgkin lymphoma (r/r) iNHL.

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+Detailed description

After completing at least 60 months (FL participants) or at least 24 months (MZL participants) of assessments in this study since the initial axicabtagene ciloleucel infusion and after agreement by the Sponsor, participants will transition to a long-term follow-up (LTFU) study, KT-US-982-5968 where they will complete the remainder of the 15 year follow-up assessments.

+Arms and interventions

Arm	Type	Interventions	Description
Axicabtagene Ciloleucel (Follicular Lymphoma)	Experimental	Biological: Axicabtagene ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine	Participants with relapsed or refractory (r/r) B-cell indolent non-Hodgkin lymphoma (iNHL) subtype of follicular lymphoma (FL) will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day for 3 days (Day -5 to Day -3). * A single infusion at a target dose of 2×10\^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)	Experimental	Biological: Axicabtagene ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine	Participants with r/r B-cell iNHL subtype of marginal zone lymphoma (MZL) will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day IV for 3 days (Day -5 to Day -3). * A single infusion at a target dose of 2×10\^6 anti-CD19 CAR transduced autologous T cells/kg on Day 0.

Axicabtagene ciloleucel (Biological), also known as Axi-cel, Yescarta®: Administered intravenously
Cyclophosphamide (Drug): Administered intravenously
Fludarabine (Drug): Administered intravenously

+Outcome measures

Primary outcomes

Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment [Up to 85.6 months]: OR:CR (complete metabolic response (CMR)+complete radiological response (CRR))+PR (partial MR response (PMR) +partial RR(PRR)).CMR: score 1(no uptake above background)/2(uptake≤mediastinum)/3(uptake >mediastinum but ≤liver)with/without a residual mass on positron emission tomography 5-point scale;no new lesions,CRR:target nodes/nodal masses regressed to ≤1.5 cm in longest transverse diameter of lesion (LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal; no new sites;bone marrow normal by morphology.PMR:score 4(uptake moderately>liver)/5(uptake markedly>liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment.PRR:≥50% decrease in sum of product of diameters up to 6 target nodes and extra-nodal sites;absent/normal,regressed,but no increase of NMLs;spleen regressed by>50% in length beyond normal. Percentages were rounded-off.

Secondary outcomes

Percentage of Participants With CR Per the Lugano Classification by Central Assessment [Up to 85.6 months]: CR is defined in outcome measure (OM)#1. Percentages were rounded-off.
ORR: Percentage of Participants With OR Per the Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy [Up to 85.6 months]: OR was defined as percentage of participants with CR + PR per the Lugano Classification for participants with 3 or more lines of prior therapy. CR and PR are defined in OM#1. Percentages were rounded-off.
Percentage of Participants With CR Per Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy [Up to 85.6 months]: CR is defined as OM#1. Percentages were rounded-off.
ORR: Percentage of Participants With OR Per the Lugano Classification by Investigator Assessment [Up to 85.6 months]: OR was defined as percentage of participants with CR + PR per the Lugano Classification. CR and PR are defined in OM#1. Percentages were rounded-off.
Percentage of Participants With Best Overall Response (BOR) Per the Lugano Classification by Central Assessment [Up to 85.6 months]: BOR was defined as percentage of participants with CR, PR, stable disease(SD), disease progression(PD), non-evaluable(NE), undefined/no disease or not done as best response to treatment by the Lugano Classification. CR and PR defined in OM#1. SD/no metabolic response(NMR):score 4(uptake moderately greater than (>) liver) or 5(uptake markedly>liver and/ or new lesions) with no significant change in fluorodeoxyglucose(FDG) uptake compared to baseline(screening), at interim time point or end of treatment; no new sites of disease should be observed. PD:score 4(uptake moderately>liver) or 5(uptake markedly>liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. Not done:no assessment at time of analysis. Percentages were rounded off.
Percentage of Participants With BOR Per the Lugano Classification by Investigator Assessment [Up to 85.6 months]: BOR was defined as the percentage of participants with CR, PR, stable disease (SD), PD, NE (not evaluable) or not done as best response to treatment by the Lugano Classification. CR and PR are defined in OM#1. SD, PD and not done are defined in OM#6. Percentages were rounded off.
Duration of Response (DOR) by Central Assessment [Up to 85.6 months]: DOR was defined only for participants who experienced an OR (CR and PR) and was the time from the first objective response to disease progression or disease-related death, whichever came first. CR and PR are defined in OM#1. PD is defined in OM#6. Kaplan-Meier (KM) estimates were used for analysis.
DOR by Investigator Assessment [Up to 85.6 months]: DOR was defined only for participants who experienced an OR (CR and PR) and was the time from the first objective response to disease progression or disease-related death, whichever came first. Definitions for CR, PR are defined in OM#1. PD is defined in OM#6. KM estimates were used for analysis.
Progression-free Survival (PFS) Per Lugano Classification by Central Assessment [Up to 85.6 months]: PFS was defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause. PD is defined in OM 6. KM estimates were used for analysis.
PFS Per Lugano Classification by Investigator Assessment [Up to 85.6 months]: PFS was defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause. PD is defined in OM 6. KM estimates were used for analysis.
Overall Survival (OS) [Up to 85.6]: OS was defined as the time from axicabtagene ciloleucel infusion to the date of death. KM estimates were used for analysis.
Time to Next Therapy [Up to 85.6 months]: Time from axicabtagene ciloleucel infusion date to the start of the subsequent new lymphoma therapy or death from any cause. KM estimates were used for analysis.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [Up to 85.6 months]: TEAE was defined as any adverse event with onset on or after the start of treatment. Percentages were rounded-off.
Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher [Up to 85.6 months]: Percentages were rounded-off.
Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher [Up to 85.6 months]: Percentages were rounded-off.
Percentage of Participants With Antibodies Against Anti-CD19 Chimeric Antigen Receptor (CAR) T Cells [Up to 85.6 months]
Levels of Anti-CD19 CAR T Cells in Blood [Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18 and Month 24]
Levels of Serum C-Reactive Protein (CRP) [Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4]
Levels of Serum Ferritin, Serum ICAM-1, Serum IL-2 R Alpha, Serum Perforin and Serum VCAM-1 [Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4]: Serum analytes: Serum Ferritin, Serum intercellular adhesion molecule-1 (ICAM-1), Serum interleukin-2 receptor (IL-2 R) alpha, Serum Perforin and Serum vascular cell adhesion molecule-1 (VCAM-1).
Levels of Serum CXCL10, Serum Granzyme B, Serum IFN-gamma, Serum IL-1 RA, Serum IL-2, Serum IL-6, Serum IL-7, Serum IL-8, Serum IL-10, Serum IL-15, Serum TNF Alpha [Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4]: Serum analytes: Serum CXCL10, Serum Granzyme B, Serum interferon (IFN)-gamma, Serum IL-1 receptor antagonist (RA), Serum IL-2, Serum IL-6, Serum IL-7, Serum IL-8, Serum IL-10, Serum IL-15, Serum tumor necrosis factor (TNF) Alpha.

+Eligibility

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

* Individual has follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has progressed after at least 2 lines of treatment with combination chemoimmunotherapy) (e.g. R-bendamustine, R-CHOP).
* Individual has (measurable disease).
* Individual has no known presence or history of central nervous system (CNS) involvement by lymphoma.
* If individual is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, individual is able to stop conventional therapy 2 weeks or 5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to planned leukapheresis.
* Individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function
* Individual is not pregnant or breastfeeding (female individuals only) and is willing to use birth control from the time of consent through 12 months following chimeric antigen receptor (CAR) T cell infusion (both male and female individuals).

Key Exclusion Criteria:

* Transformed FL or MZL
* Small lymphocytic lymphoma
* Histological Grade 3b FL
* Individual will have undergone autologous transplant within 6 weeks of planned leukapheresis or has undergone allogeneic transplant.
* Individual has evidence of involvement of the heart by lymphoma or requirement for urgent therapy due to ongoing or impending oncologic emergency (e.g. mass effect, tumor lysis syndrome, etc.)

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

+Posted results

Participant flow

Milestone	Axicabtagene Ciloleucel (Follicular Lymphoma)	Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
Started	127	31
Completed	0	0
Not completed	127	31

Outcome results

Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment (Primary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 92 (86 to 96); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 69 (49 to 85)
Percentage of Participants With CR Per the Lugano Classification by Central Assessment (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 78 (70 to 85); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 52 (33 to 71)
ORR: Percentage of Participants With OR Per the Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 91 (83 to 96); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 75 (51 to 91)
Percentage of Participants With CR Per Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 79 (68 to 87); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 60 (36 to 81)
ORR: Percentage of Participants With OR Per the Lugano Classification by Investigator Assessment (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 94 (88 to 97); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 77 (59 to 90)
Percentage of Participants With Best Overall Response (BOR) Per the Lugano Classification by Central Assessment (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 78 (70 to 85); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 52 (33 to 71)
Percentage of Participants With BOR Per the Lugano Classification by Investigator Assessment (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 79 (71 to 85); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 65 (45 to 81)
Duration of Response (DOR) by Central Assessment (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) 38.6 (NA to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) NA (8.2 to NA)
DOR by Investigator Assessment (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) 60.4 (36.6 to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) NA (13.9 to NA)
Progression-free Survival (PFS) Per Lugano Classification by Central Assessment (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) 40.2 (28.9 to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 18.3 (12.1 to NA)
PFS Per Lugano Classification by Investigator Assessment (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) 58.2 (30.9 to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) NA (12.4 to NA)
Overall Survival (OS) (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) NA (NA to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) NA (NA to NA)
Time to Next Therapy (Secondary), Median, months: Axicabtagene Ciloleucel (Follicular Lymphoma) NA (37.8 to NA); Axicabtagene Ciloleucel (Marginal Zone Lymphoma) NA (12.1 to NA)
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 99; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 100
Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 0; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 0
Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 33; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 39
Percentage of Participants With Antibodies Against Anti-CD19 Chimeric Antigen Receptor (CAR) T Cells (Secondary), Number, percentage of participants: Axicabtagene Ciloleucel (Follicular Lymphoma) 0; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 0
Levels of Anti-CD19 CAR T Cells in Blood (Secondary), Mean, cells/μL: Axicabtagene Ciloleucel (Follicular Lymphoma) 101.49 +/- 220.01; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 120.07 +/- 394.91
Levels of Serum C-Reactive Protein (CRP) (Secondary), Mean, mg/L: Axicabtagene Ciloleucel (Follicular Lymphoma) 22.36 +/- 40.60; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 19.87 +/- 28.62
Levels of Serum Ferritin, Serum ICAM-1, Serum IL-2 R Alpha, Serum Perforin and Serum VCAM-1 (Secondary), Mean, ng/L: Axicabtagene Ciloleucel (Follicular Lymphoma) 330.54 +/- 398.03; Axicabtagene Ciloleucel (Marginal Zone Lymphoma) 207.63 +/- 218.42
1 more outcome measures not shown.

Adverse events

Time frame: Up to 85.6 months

Arm	Deaths	Serious adverse events	Other adverse events
Axicabtagene Ciloleucel: Follicular Lymphoma	36/127 (28.3%)	65/124 (52.4%)	123/124 (99.2%)
Axicabtagene Ciloleucel: Marginal Zone Lymphoma	8/31 (25.8%)	19/28 (67.9%)	28/28 (100.0%)
Axicabtagene Ciloleucel: Retreatment (FL)	5/14 (35.7%)	5/14 (35.7%)	13/14 (92.9%)
Axicabtagene Ciloleucel: Retreatment (MZL)	0/2 (0.0%)	1/2 (50.0%)	2/2 (100.0%)

Serious adverse events by term

Term	Organ system	Axicabtagene Ciloleucel: Follicular Lymphoma	Axicabtagene Ciloleucel: Marginal Zone Lymphoma	Axicabtagene Ciloleucel: Retreatment (FL)	Axicabtagene Ciloleucel: Retreatment (MZL)
Anaemia	Blood and lymphatic system disorders	1/124	0/28	0/14	0/2
Febrile neutropenia	Blood and lymphatic system disorders	2/124	3/28	0/14	0/2
Lymph node pain	Blood and lymphatic system disorders	1/124	0/28	0/14	0/2
Neutropenia	Blood and lymphatic system disorders	2/124	1/28	0/14	0/2
Pancytopenia	Blood and lymphatic system disorders	1/124	0/28	0/14	0/2
Atrial fibrillation	Cardiac disorders	0/124	2/28	0/14	0/2
Cardiac failure	Cardiac disorders	1/124	0/28	0/14	0/2
Sinus tachycardia	Cardiac disorders	1/124	0/28	0/14	0/2
Stress cardiomyopathy	Cardiac disorders	1/124	0/28	0/14	0/2
Tachycardia	Cardiac disorders	2/124	0/28	0/14	0/2
Blindness	Eye disorders	1/124	0/28	0/14	0/2
Vision blurred	Eye disorders	1/124	0/28	0/14	0/2
Abdominal pain upper	Gastrointestinal disorders	1/124	0/28	0/14	0/2
Colitis	Gastrointestinal disorders	1/124	0/28	0/14	0/2
Diverticular perforation	Gastrointestinal disorders	1/124	0/28	0/14	0/2
Retroperitoneal haemorrhage	Gastrointestinal disorders	1/124	0/28	0/14	0/2
Stomatitis	Gastrointestinal disorders	0/124	1/28	0/14	0/2
Vomiting	Gastrointestinal disorders	1/124	0/28	0/14	0/2
Chills	General disorders	1/124	1/28	0/14	0/2
Fatigue	General disorders	1/124	1/28	0/14	0/2
Gait disturbance	General disorders	1/124	0/28	0/14	0/2
Influenza like illness	General disorders	0/124	1/28	0/14	0/2
Malaise	General disorders	1/124	0/28	0/14	0/2
Mucosal inflammation	General disorders	1/124	0/28	0/14	0/2
Multiple organ dysfunction syndrome	General disorders	2/124	0/28	0/14	0/2
Pyrexia	General disorders	16/124	6/28	0/14	0/2
Bacterial infection	Infections and infestations	1/124	0/28	0/14	0/2
Bronchitis	Infections and infestations	1/124	0/28	0/14	0/2
Cellulitis	Infections and infestations	0/124	1/28	0/14	0/2
Clostridium difficile colitis	Infections and infestations	1/124	0/28	0/14	0/2
Coccidioidomycosis	Infections and infestations	0/124	1/28	0/14	0/2
Covid-19	Infections and infestations	3/124	1/28	0/14	0/2
Covid-19 pneumonia	Infections and infestations	1/124	0/28	0/14	0/2
Cytomegalovirus infection reactivation	Infections and infestations	0/124	1/28	0/14	0/2
Escherichia infection	Infections and infestations	1/124	0/28	0/14	0/2
Influenza	Infections and infestations	2/124	0/28	0/14	0/2
Kidney infection	Infections and infestations	1/124	0/28	0/14	0/2
Lymph gland infection	Infections and infestations	0/124	1/28	0/14	0/2
Mycobacterium kansasii infection	Infections and infestations	1/124	0/28	0/14	0/2
Parainfluenzae virus infection	Infections and infestations	0/124	0/28	1/14	0/2
Pneumonia	Infections and infestations	10/124	3/28	0/14	0/2
Pneumonia streptococcal	Infections and infestations	1/124	0/28	0/14	0/2
Progressive multifocal leukoencephalopathy	Infections and infestations	0/124	0/28	1/14	0/2
Prostate infection	Infections and infestations	1/124	0/28	0/14	0/2
Sepsis	Infections and infestations	1/124	1/28	1/14	0/2
Sinusitis	Infections and infestations	1/124	0/28	0/14	0/2
Staphylococcal bacteraemia	Infections and infestations	0/124	0/28	1/14	0/2
Staphylococcal infection	Infections and infestations	1/124	0/28	0/14	0/2
Systemic candida	Infections and infestations	1/124	0/28	0/14	0/2
Upper respiratory tract infection	Infections and infestations	0/124	1/28	0/14	0/2
Urinary tract infection	Infections and infestations	3/124	0/28	0/14	1/2
Fall	Injury, poisoning and procedural complications	0/124	1/28	0/14	0/2
Hip fracture	Injury, poisoning and procedural complications	0/124	1/28	0/14	0/2
Tracheal obstruction	Injury, poisoning and procedural complications	0/124	1/28	0/14	0/2
Alanine aminotransferase increased	Investigations	0/124	1/28	0/14	0/2
Aspartate aminotransferase increased	Investigations	1/124	1/28	0/14	0/2
Blood alkaline phosphatase increased	Investigations	0/124	1/28	0/14	0/2
Blood bilirubin increased	Investigations	1/124	1/28	0/14	0/2
Blood fibrinogen decreased	Investigations	0/124	1/28	0/14	0/2
Clostridium test positive	Investigations	1/124	0/28	0/14	0/2

57 more terms not shown.

Other adverse events by term

Term	Organ system	Axicabtagene Ciloleucel: Follicular Lymphoma	Axicabtagene Ciloleucel: Marginal Zone Lymphoma	Axicabtagene Ciloleucel: Retreatment (FL)	Axicabtagene Ciloleucel: Retreatment (MZL)
Anaemia	Blood and lymphatic system disorders	46/124	14/28	2/14	1/2
Leukopenia	Blood and lymphatic system disorders	19/124	4/28	0/14	0/2
Lymphopenia	Blood and lymphatic system disorders	10/124	3/28	0/14	0/2
Neutropenia	Blood and lymphatic system disorders	47/124	9/28	2/14	0/2
Thrombocytopenia	Blood and lymphatic system disorders	27/124	3/28	0/14	0/2
Sinus bradycardia	Cardiac disorders	7/124	2/28	0/14	0/2
Sinus tachycardia	Cardiac disorders	41/124	8/28	3/14	2/2
Tachycardia	Cardiac disorders	14/124	4/28	1/14	0/2
Dry eye	Eye disorders	0/124	2/28	0/14	0/2
Abdominal distension	Gastrointestinal disorders	3/124	0/28	1/14	0/2
Abdominal pain	Gastrointestinal disorders	16/124	4/28	0/14	0/2
Constipation	Gastrointestinal disorders	35/124	7/28	1/14	2/2
Diarrhoea	Gastrointestinal disorders	33/124	9/28	3/14	0/2
Dry mouth	Gastrointestinal disorders	6/124	3/28	0/14	0/2
Dysphagia	Gastrointestinal disorders	6/124	2/28	0/14	0/2
Nausea	Gastrointestinal disorders	45/124	17/28	5/14	2/2
Vomiting	Gastrointestinal disorders	28/124	9/28	0/14	0/2
Catheter site pruritus	General disorders	0/124	0/28	1/14	0/2
Chills	General disorders	32/124	10/28	3/14	0/2
Fatigue	General disorders	50/124	15/28	3/14	2/2
Gait disturbance	General disorders	9/124	2/28	0/14	0/2
Malaise	General disorders	7/124	2/28	1/14	0/2
Oedema peripheral	General disorders	10/124	4/28	1/14	1/2
Pain	General disorders	17/124	3/28	0/14	1/2
Pyrexia	General disorders	99/124	24/28	8/14	2/2
Hypogammaglobulinaemia	Immune system disorders	22/124	6/28	0/14	0/2
Coronavirus infection	Infections and infestations	0/124	0/28	1/14	0/2
Covid-19	Infections and infestations	4/124	2/28	1/14	0/2
Herpes zoster	Infections and infestations	5/124	2/28	0/14	0/2
Influenza	Infections and infestations	3/124	3/28	0/14	0/2
Nasopharyngitis	Infections and infestations	2/124	2/28	0/14	0/2
Oral candidiasis	Infections and infestations	9/124	4/28	0/14	0/2
Oral herpes	Infections and infestations	0/124	0/28	1/14	0/2
Pneumonia	Infections and infestations	10/124	4/28	0/14	0/2
Rhinovirus infection	Infections and infestations	5/124	1/28	2/14	0/2
Sinusitis	Infections and infestations	9/124	4/28	0/14	0/2
Tooth infection	Infections and infestations	1/124	2/28	0/14	0/2
Upper respiratory tract infection	Infections and infestations	14/124	8/28	0/14	0/2
Urinary tract infection	Infections and infestations	8/124	4/28	0/14	0/2
Vulvovaginal mycotic infection	Infections and infestations	0/124	0/28	0/14	1/2
Administration related reaction	Injury, poisoning and procedural complications	0/124	0/28	1/14	0/2
Contusion	Injury, poisoning and procedural complications	1/124	2/28	0/14	0/2
Fall	Injury, poisoning and procedural complications	3/124	3/28	0/14	0/2
Infusion related reaction	Injury, poisoning and procedural complications	1/124	2/28	2/14	0/2
Alanine aminotransferase increased	Investigations	11/124	6/28	0/14	0/2
Aspartate aminotransferase increased	Investigations	10/124	3/28	0/14	0/2
Blood fibrinogen decreased	Investigations	3/124	3/28	0/14	0/2
Lymphocyte count decreased	Investigations	8/124	1/28	1/14	0/2
Neutrophil count decreased	Investigations	30/124	14/28	2/14	1/2
Platelet count decreased	Investigations	19/124	6/28	1/14	1/2
Weight decreased	Investigations	5/124	1/28	1/14	0/2
White blood cell count decreased	Investigations	23/124	9/28	2/14	1/2
Decreased appetite	Metabolism and nutrition disorders	28/124	9/28	6/14	1/2
Hyperglycaemia	Metabolism and nutrition disorders	6/124	6/28	0/14	0/2
Hyperuricaemia	Metabolism and nutrition disorders	0/124	2/28	0/14	0/2
Hypoalbuminaemia	Metabolism and nutrition disorders	13/124	4/28	0/14	0/2
Hypocalcaemia	Metabolism and nutrition disorders	22/124	6/28	0/14	0/2
Hypokalaemia	Metabolism and nutrition disorders	22/124	6/28	1/14	1/2
Hypomagnesaemia	Metabolism and nutrition disorders	17/124	5/28	0/14	0/2
Hyponatraemia	Metabolism and nutrition disorders	14/124	5/28	0/14	0/2

52 more terms not shown.

+Locations (19)

Facility	City	Country
Banner MD Anderson Cancer Center	Gilbert, Arizona	United States
USC Norris Comprehensive Cancer Center	Los Angeles, California	United States
University of California Los Angeles	Los Angeles, California	United States
Georgetown Lombardi Comprehensive Cancer Center	Washington D.C., District of Columbia	United States
University of Miami Hospital and Clinics	Miami, Florida	United States
H Lee Moffitt Cancer Center	Tampa, Florida	United States
Dana Farber Cancer Institute	Boston, Massachusetts	United States
Hackensack University Medical Center - John Theurer Cancer Center	Hackensack, New Jersey	United States
Columbia University Medical Center	New York, New York	United States
University of Rochester Medical Center (URMC)	Rochester, New York	United States
Ohio State University Medical Center	Cleveland, Ohio	United States
Fox Chase Cancer Center	Philadelphia, Pennsylvania	United States
UPMC Hillman Cancer Center	Pittsburgh, Pennsylvania	United States
Sarah Cannon Research Institute	Nashville, Tennessee	United States
Vanderbilt University Medical Center	Nashville, Tennessee	United States
MD Anderson Cancer Center	Houston, Texas	United States
Fred Hutchinson Cancer Research Center	Seattle, Washington	United States
Centre Hospitalier Régional Universitaire de Lille	Lille	France
Centre Hospitalier Lyon Sud	Pierre-Bénite	France

+Publications

Jacobson CA, Chavez JC, Sehgal AR, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL). Conference Proceedings of the American Society of Clinical Oncology 2020
Jacobson CA, Chavez JC, Sehgal AR, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL) [Abstract]. Conference Proceedings of the Society of Hematologic Oncology 2020.
Jacobson CA, Chavez JC, Sehgal AR, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL) [Abstract]. Clinical Lymphoma, Myeloma and Leukemia 2020;20 (1 Suppl):S278.
Jacobson C, Chavez JC, Sehgal AR, et al. Primary analysis of Zuma-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL). Blood 2020;136 (1 Suppl):40-41.
Chavez JC, Jacobson CA, Sehgal AR, et al. Retreatment with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma in ZUMA-5. Blood 2020;136 (1 Suppl):34.
Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Yakoub-Agha I, Oluwole OO, Fung HCH, Rosenblatt J, Rossi JM, Goyal L, Plaks V, Yang Y, Vezan R, Avanzi MP, Neelapu SS. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):91-103. doi: 10.1016/S1470-2045(21)00591-X. Epub 2021 Dec 8. PMID 34895487
Chavez JC, Jacobson CA, Sehgal A, et al. Updated outcomes with axicabtagene ciloleucel (axi-cel) retreatment (reTx) in patients (pts) with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5. J Clin Oncol 2021;39 (15 suppl):7548.
Chavez JC, Jacobson CA, Sehgal AR, et al. Retreatment with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (r/r) indolent non-hodgkin lymphoma (iNHL) in ZUMA-5 [Oral abstract]. Transplantation and Cellular Therapy 2021;27 (Issue 3, Supplement):S43, ISSN 2666-6367
Chavez JC, Jacobson CA, Sehgal AR, et al. Retreatment with axicabtagene ciloleucel in patients with relapsed/refractory indolent non-hodgkin lymphoma in ZUMA-5 [Oral abstract]. British Journal of Heamatology 2021;193. Abstract BSH2021-PO-149.
Chavez JC, Jacobson CA, Sehgal AR, et al. Updated outcomes with axicabtagene ciloleucel (axi-cel) retreatment in patients with relapsed/refractory indolent non-Hodgkin lymphoma in ZUMA-5 [Abstract]. European Hematology Association (EHA) 2021:325549.
Ghione P, Patel A, Bobillo S, et al. A comparison of clinical outcomes from Zuma-5 (axicabtagene ciloleucel) and the international scholar-5 external control cohort in relapsed/refractory follicular lymphoma (R/R/FL) [Abstract]. European Hematology Association (EHA) Virtual; 2021 09-17 June.
Ghione P, Palomba ML, Ghesquieres H, Bobillo S, Patel AR, Nahas M, Kanters S, Deighton K, Hatswell A, Ma L, Limbrick-Oldfield EH, Snider JT, Wade SW, Riberio MT, Radford J, Beygi S, Gribben J. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023 Mar 1;108(3):822-832. doi: 10.3324/haematol.2022.281421. PMID 36263843
Jacobson CA, Chavez JC, Sehgal A, et al. Outcomes in ZUMA-5 with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) who had the high-risk feature of progression within 24 months from initiation of first anti-CD20-containing chemoimmunotherapy (POD24). J Clin Oncol 2021a;39 (15 Suppl):7515
Jacobson CA, Chavez JC, Sehgal AR, et al. Outcomes in Zuma-5 with axicabtagene ciloleucel in patients with relapsed/refractory indolent non-Hodgkin lymphoma who had the high-risk feature of early progression after first chemoimmunotherapy [Abstract]. European Hematology Association (EHA) Virtual; 2021b 09-17 June.
Jacobson CA, Chavez JC, Sehgal AR, et al. Primary analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL) [Oral abstract 69]. Transplantation and Cellular Therapy 2021; 27 (Issue 3, Supplement): S67-S68, ISSN 2666-6367
Jacobson CA, Chavez JC, Sehgal AR, et al. Primary analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel in patients with relapsed/refractory indolent non-hodgkin lymphoma [Oral abstract]. British Journal of Heamatology 2021, BSH2021-OR-036.
Neelapu SS, Chavez JC, Sehgal AR, et al. Long-term follow-up analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) [Abstract 93]. Blood 2021;138 (1 Suppl)
Plaks V, Chou J, Goyal L, et al. Axicabtagene ciloleucel (axi-cel) product attributes and immune biomarkers associated with clinical outcomes in patients (pts) with relapsed/refractory R/R) indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5 [Abstract CT036]. Cancer Res 2021;81 (13 Suppl).
Kanters S, Ball G, Kahl B, Wiesinger A, Limbrick-Oldfield EH, Sudhindra A, Snider JT, Patel AR. Clinical outcomes in patients relapsed/refractory after >/=2 prior lines of therapy for follicular lymphoma: a systematic literature review and meta-analysis. BMC Cancer. 2023 Jan 23;23(1):74. doi: 10.1186/s12885-023-10546-6. PMID 36690960
Palomba ML, Ghione P, Patel AR, et al. A comparison of clinical outcomes from updated ZUMA-5 (axicabtagene ciloleucel) and the international scholar-5 external control cohort in relapsed/refractory follicular lymphoma (R/R FL) [Abstract PB1571]. Blood 2021;138 (1 Suppl):3543.
Neelapu SS, Chavez JC, Sehgal AR, et al. Long-term follow-up analysis of Zuma-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL) [Abstract 75]. Transplantation and Cellular Therapy 2022;28 (Issue 3, Supplement):S64-S65, ISSN 2666-6367.
Neelapu SS, Chavez JC, Sehgal AR, et al. Long-term analysis of ZUMA-5 phase 2 study of axicabtagene ciloleucel in patients with indolent non-Hodgkin lymphoma [Oral presentation O3-5]. 2022 Japanese Society of Medical Oncology - 19th Scientific Meeting
Hatswell AJ, Deighton K, Snider JT, Brookhart MA, Faghmous I, Patel AR. Approaches to Selecting "Time Zero" in External Control Arms with Multiple Potential Entry Points: A Simulation Study of 8 Approaches. Med Decis Making. 2022 Oct;42(7):893-905. doi: 10.1177/0272989X221096070. Epub 2022 May 6. PMID 35514320
Ghione P, Palomba ML, Patel AR, Bobillo S, Deighton K, Jacobson CA, Nahas M, Hatswell AJ, Jung AS, Kanters S, Snider JT, Neelapu SS, Ribeiro MT, Brookhart MA, Ghesquieres H, Radford J, Gribben JG. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022 Aug 25;140(8):851-860. doi: 10.1182/blood.2021014375. PMID 35679476
Neelapu SS, Chavez JC, Sehgal AR, et al. 3-Year follow-up analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL). Blood 2022;140 (1 Suppl):10380-10383.
Oluwole OO, Ray MD, Rosettie KL, Ball G, Jacob J, Bilir SP, Patel AR, Jacobson CA. Cost-Effectiveness of Axicabtagene Ciloleucel for Adult Patients With Relapsed or Refractory Follicular Lymphoma in the United States. Value Health. 2024 Aug;27(8):1030-1038. doi: 10.1016/j.jval.2024.04.003. Epub 2024 Apr 17. PMID 38641058
Ghione P, Palomba ML, Ray MD, et al. A 3-year follow-up comparison of clinical outcomes from Zuma-5 (axicabtagene ciloleucel) and the international Scholar-5 external control cohort in relapsed/refractory follicular lymphoma (R/R FL). Blood 2022;140 (1 Suppl):4676-4677.
Neelapu SS, Chavez JC, Sehgal AR, et al. 3-Year follow-up analysis of Zuma-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL) [Abstract 500]. Transplantation and Cellular Therapy 2023;29 (Issue 2, Supplement):S374, ISSN 2666-6367
Palomba ML, Ghione P, Patel AR, Nahas M, Beygi S, Hatswell AJ, Kanters S, Limbrick-Oldfield EH, Wade SW, Ray MD, Owen J, Neelapu SS, Gribben J, Radford J, Bobillo S. A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Expert Rev Anticancer Ther. 2023 Feb;23(2):199-206. doi: 10.1080/14737140.2023.2171994. Epub 2023 Feb 10. PMID 36723678
Patel AR, Limbrick-Oldfield EH, Kanters S, et al., The prognostic value of progressing within 24 months of frontline chemoimmunotherapy (POD24) in relapsed/refractory (R/R) follicular lymphoma (FL)-a SCHOLAR-5 analysis. Hematological Oncology 2023;41:376-377.
Ray MD, Kanters S, Beygi S, et al. Matching-adjusted indirect comparison of axicabtagene ciloleucel versus mosunetuzumab in relapsed/refractory follicular lymphoma patients after 2 prior systemic treatments. Hematological Oncology 2023;41:522-523
Neelapu SS, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: 4-year follow-up from the phase 2 ZUMA-5 trial. Blood 2023;142 (1 Suppl):4868.
Bachy E, Neelapu SS, Chavez JC, et al. A retrospective intra-patient analysis from ZUMA-5: Axicabtagene ciloleucel (axi-cel) compared with prior standard-of-care therapy in patients with relapsed/refractory follicular lymphoma. Blood 2023;142 (1 Suppl):4865.
Gribben JG, Ghione P, Palomba ML, et al. An updated comparison of clinical outcomes from 4-year follow-up of Zuma-5 (axicabtagene ciloleucel) and the international Scholar-5 external control cohort in relapsed/refractory follicular lymphoma. Blood 2023;142 (1 Suppl):4869.
Eklund O, Hedlöf Kanje V, Doble B, et al. EE536 Cost-effectiveness of axicabtagene ciloleucel (axi-cel) vs standard of care for adult patients with relapsed or refractory follicular lymphoma as 4TH or later line treatment in Sweden. Value in Health 2023;26 (Issue 12, Supplement):S155, ISSN 1098-3015.
Ghione P, Palomba ML, Ray MD, Limbrick-Oldfield EH, Owen J, Kanters S, Bobillo S, Ribiero MT, Jacobson CA, Neelapu SS, Ghesquieres H, Nahas M, Beygi S, Patel AR, Gribben JG. A Comparison of 3-Year Follow-up of ZUMA-5 (Axicabtagene Ciloleucel) With SCHOLAR-5 in Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 May;24(5):e191-e195.e6. doi: 10.1016/j.clml.2024.01.011. Epub 2024 Jan 24. PMID 38365528
Neelapu SS, Chavez JC, Sehgal AR, Epperla N, Ulrickson M, Bachy E, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Oluwole OO, Yakoub-Agha I, Khanal R, Rosenblatt J, Korn R, Peng W, Lui C, Wulff J, Shen R, Poddar S, Jung AS, Miao H, Beygi S, Jacobson CA. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024 Feb 8;143(6):496-506. doi: 10.1182/blood.2023021243. PMID 37879047
Oluwole OO, Ray MD, Zur RM, Ferrufino CP, Doble B, Patel AR, Bilir SP. Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States. Front Immunol. 2024 May 24;15:1393939. doi: 10.3389/fimmu.2024.1393939. eCollection 2024. PMID 38855109
Ray MD, Kanters S, Beygi S, Best T, Wulff J, Limbrick-Oldfield E, Patel AR, Oluwole OO. Matching-Adjusted Indirect Comparisons of Axicabtagene Ciloleucel to Mosunetuzumab for the Treatment of Relapsed/Refractory Follicular Lymphoma. Transplant Cell Ther. 2024 Sep;30(9):885.e1-885.e11. doi: 10.1016/j.jtct.2024.06.016. Epub 2024 Jun 19. PMID 38901633
Neelapu SS, Chavez JC, Sehgal AR, et al. 5-year follow-up analysis from ZUMA-5: A phase 2 trial of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Blood 2024;144 (1 Suppl):864.
Poddar S, Yan J, Tiwari G, et al. Impact of inflammation, tumor and product attributes on clinical outcomes in patients with relapsed/refractory follicular lymphoma treated with axicabtagene ciloleucel. Blood 2024;144 (1 Suppl):4368
Limbrick-Oldfield EH, Kanters S, Ray MD, Best T, Palivela M, Beygi S, Patel AR, Gribben JG, Ghione P. The prognostic value of POD24 in relapsed/refractory follicular lymphoma-A SCHOLAR-5 analysis. EJHaem. 2025 Feb 6;6(1):e1104. doi: 10.1002/jha2.1104. eCollection 2025 Feb. PMID 39917356
Results publication: Neelapu SS, Nikolajeva O, Jacobson CA. Plain language summary of the ZUMA-5 study of axicabtagene ciloleucel for people with relapsed or refractory slow-growing non-Hodgkin lymphoma. Future Oncol. 2026 Sep 16:1-17. doi: 10.1080/14796694.2026.2719395. Online ahead of print. PMID 42745632
Results publication: Neelapu SS, Chavez JC, Sehgal AR, Epperla N, Ulrickson ML, Bachy E, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Oluwole OO, Yakoub-Agha I, Khanal R, Rosenblatt JD, Wulff J, Shen RR, Zhang W, Poddar S, Miao H, Nikolajeva O, Jacobson CA. Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2025 Nov 20;43(33):3573-3577. doi: 10.1200/JCO-25-00668. Epub 2025 Oct 16. PMID 41100801
Results publication: Poddar S, Yan J, Tiwari G, Rinchai D, Budka J, Zhang W, Peng W, Salunkhe S, Davis M, Song Q, Beygi S, Miao H, Mattie M, Shen RS, Jacobson CA, Bedognetti D, Filosto S, Neelapu SS. Clinical, tumor, and product features associated with outcomes after axicabtagene ciloleucel therapy in follicular lymphoma. J Clin Invest. 2025 Aug 15;135(16):e181893. doi: 10.1172/JCI181893. eCollection 2025 Aug 15. PMID 40536814
Results publication: Chartier M, Filosto S, Peyret T, Chiney M, Milletti F, Budka J, Ndi A, Dong J, Vardhanabhuti S, Mao D, Duffull S, Dodds M, Shen R. Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma. Clin Pharmacokinet. 2024 Sep;63(9):1283-1299. doi: 10.1007/s40262-024-01413-z. Epub 2024 Sep 6. PMID 39240498

+Study documents

Study Protocol (PDF, 2024-01-29)
Statistical Analysis Plan (PDF, 2020-08-03)

+Investigators

Kite Study Director, Study director, Kite, A Gilead Company

+Funding

NIH grants: 2023, 2017

My Notes

Public

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