NCT03105336 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-12-23

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Duration of Response (DOR) by Central Assessment

→

outcome · POSTED

DOR by Investigator Assessment

→

outcome · POSTED

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

→

outcome · POSTED

PFS Per Lugano Classification by Investigator Assessment

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Time to Next Therapy

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Levels of Anti-CD19 CAR T Cells in Blood

→

outcome · POSTED

Levels of Serum C-Reactive Protein (CRP)

→

outcome · POSTED

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

→

outcome · POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Biological: Axicabtagene ciloleucel
Drug: Cyclophosphamide
Drug: Fludarabine
label
Axicabtagene Ciloleucel (Follicular Lymphoma)
type
EXPERIMENTAL
description
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.
intervention Names
Biological: Axicabtagene ciloleucel
Drug: Cyclophosphamide
Drug: Fludarabine
label
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
type
EXPERIMENTAL

interventions

arm Group Labels
Axicabtagene Ciloleucel (Follicular Lymphoma)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
description
Administered intravenously
name
Axicabtagene ciloleucel
other Names
Axi-cel
Yescarta®
type
BIOLOGICAL
arm Group Labels
Axicabtagene Ciloleucel (Follicular Lymphoma)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
description
Administered intravenously
name
Cyclophosphamide
type
DRUG
arm Group Labels
Axicabtagene Ciloleucel (Follicular Lymphoma)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
description
Administered intravenously
name
Fludarabine
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 159
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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

secondary Outcomes

description
CR is defined in outcome measure (OM)#1. Percentages were rounded-off.
measure
Percentage of Participants With CR Per the Lugano Classification by Central Assessment
time Frame
Up to 85.6 months
description
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.
measure
ORR: Percentage of Participants With OR Per the Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy
time Frame
Up to 85.6 months
description
CR is defined as OM#1. Percentages were rounded-off.
measure
Percentage of Participants With CR Per Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy
time Frame
Up to 85.6 months
description
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.
measure
ORR: Percentage of Participants With OR Per the Lugano Classification by Investigator Assessment
time Frame
Up to 85.6 months
description
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.
measure
Percentage of Participants With Best Overall Response (BOR) Per the Lugano Classification by Central Assessment
time Frame
Up to 85.6 months
description
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.
measure
Percentage of Participants With BOR Per the Lugano Classification by Investigator Assessment
time Frame
Up to 85.6 months
description
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.
measure
Duration of Response (DOR) by Central Assessment
time Frame
Up to 85.6 months
description
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.
measure
DOR by Investigator Assessment
time Frame
Up to 85.6 months
description
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.
measure
Progression-free Survival (PFS) Per Lugano Classification by Central Assessment
time Frame
Up to 85.6 months
description
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.
measure
PFS Per Lugano Classification by Investigator Assessment
time Frame
Up to 85.6 months
description
OS was defined as the time from axicabtagene ciloleucel infusion to the date of death. KM estimates were used for analysis.
measure
Overall Survival (OS)
time Frame
Up to 85.6
description
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.
measure
Time to Next Therapy
time Frame
Up to 85.6 months

Full study description

brief 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.
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.

Source references

references

citation
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
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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
type
BACKGROUND