AzTrials
AzTrials

Follicular LymphomaPhase 2ZUMA-5NCT03105336

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

A Phase 2 study testing Axicabtagene ciloleucel, Cyclophosphamide and Fludarabine in people with Follicular Lymphoma and Marginal Zone Lymphoma, run by Kite, A Gilead Company at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Axicabtagene ciloleucel, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
159 participants
Where
19 sitesin 2 countries
Study dates
6 Jun 2017to 20 Dec 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

United States17 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Medical Center

    Cleveland, Ohio, 44106

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Hackensack University Medical Center - John Theurer Cancer Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Miami Hospital and Clinics

    Miami, Florida, 33136

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Columbia University Medical Center

    New York, New York, 10032

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • University of Rochester Medical Center (URMC)

    Rochester, New York, 14642

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • H Lee Moffitt Cancer Center

    Tampa, Florida, 33612

  • Georgetown Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

France2 sites

  • Centre Hospitalier Régional Universitaire de Lille

    Lille, 59037

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

Other trials in France

About this study

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

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.

Read the 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.

Being tested
Axicabtagene ciloleucel, Cyclophosphamide, Fludarabine
Medical subject headings
Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Axicabtagene ciloleucelBiological

    Also called Axi-cel, Yescarta®

    Administered intravenously

  • CyclophosphamideDrug

    Administered intravenously

  • FludarabineDrug

    Administered intravenously

Study groups in NCT03105336
Study groupRoleWhat they receive
Axicabtagene Ciloleucel (Follicular Lymphoma)ExperimentalParticipants 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.
Receives: Biological: Axicabtagene ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)ExperimentalParticipants 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.
Receives: Biological: Axicabtagene ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment

    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.

    Measured: Up to 85.6 months

Secondary outcomes (20)

  1. Percentage of Participants With CR Per the Lugano Classification by Central Assessment

    CR is defined in outcome measure (OM)#1. Percentages were rounded-off.

    Measured: Up to 85.6 months

  2. ORR: Percentage of Participants With OR Per the Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy

    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.

    Measured: Up to 85.6 months

  3. Percentage of Participants With CR Per Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy

    CR is defined as OM#1. Percentages were rounded-off.

    Measured: Up to 85.6 months

  4. ORR: Percentage of Participants With OR Per the Lugano Classification by Investigator Assessment

    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.

    Measured: Up to 85.6 months

  5. Percentage of Participants With Best Overall Response (BOR) Per the Lugano Classification by Central Assessment

    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.

    Measured: Up to 85.6 months

  6. Percentage of Participants With BOR Per the Lugano Classification by Investigator Assessment

    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.

    Measured: Up to 85.6 months

  7. Duration of Response (DOR) by Central Assessment

    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.

    Measured: Up to 85.6 months

  8. DOR by Investigator Assessment

    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.

    Measured: Up to 85.6 months

  9. Progression-free Survival (PFS) Per Lugano Classification by Central Assessment

    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.

    Measured: Up to 85.6 months

  10. PFS Per Lugano Classification by Investigator Assessment

    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.

    Measured: Up to 85.6 months

  11. Overall Survival (OS)

    OS was defined as the time from axicabtagene ciloleucel infusion to the date of death. KM estimates were used for analysis.

    Measured: Up to 85.6

  12. Time to Next Therapy

    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.

    Measured: Up to 85.6 months

  13. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

    TEAE was defined as any adverse event with onset on or after the start of treatment. Percentages were rounded-off.

    Measured: Up to 85.6 months

  14. Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher

    Percentages were rounded-off.

    Measured: Up to 85.6 months

  15. Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher

    Percentages were rounded-off.

    Measured: Up to 85.6 months

  16. Percentage of Participants With Antibodies Against Anti-CD19 Chimeric Antigen Receptor (CAR) T Cells

    Measured: Up to 85.6 months

  17. Levels of Anti-CD19 CAR T Cells in Blood

    Measured: Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18 and Month 24

  18. Levels of Serum C-Reactive Protein (CRP)

    Measured: Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4

  19. Levels of Serum Ferritin, Serum ICAM-1, Serum IL-2 R Alpha, Serum Perforin and Serum VCAM-1

    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).

    Measured: Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4

  20. 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

    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.

    Measured: Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2017
  2. Study start6 Jun 2017
  3. Primary completion20 Dec 2024
  4. Study completion20 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03105336
Sponsor's protocol ID
KTE-C19-105
Other IDs
2017-001912-13, 2023-505169-10, 2023, 2017
Acronym
ZUMA-5
Status last verified
Dec 2025
First submitted
3 Apr 2017
Last updated
23 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment

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.

    PubMed 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.

    PubMed 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axicabtagene ciloleucel, Cyclophosphamide and Fludarabine in people with Follicular Lymphoma and Marginal Zone Lymphoma, run by Kite, A Gilead Company at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment (time frame: Up to 85.6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03105336, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in