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Refractory Large B-cell LymphomaPhase 2ZUMA-14NCT04002401

Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma

A Phase 2 study testing Axicabtagene Ciloleucel, Rituximab and Fludarabine in people with Refractory Large B-cell Lymphoma, run by Kite, A Gilead Company at 14 sites in United States.

Completed

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

Official record
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Trial summary

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Large B-cell Lymphoma
What is being tested?
Axicabtagene Ciloleucel, Rituximab and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
14 sitesUnited States
Study dates
5 Nov 2019to 30 Jan 2023
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

  • Histologically confirmed large B-cell lymphoma
  • Chemotherapy-refractory disease, defined as one or more of the following:
  • No response to first-line therapy (primary refractory disease)
  • No response to second or greater lines of therapy OR
  • Refractory after autologous stem cell transplant (ASCT)
  • At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).
Show all 11Show fewer
  • Individuals must have received adequate prior therapy, including at a minimum:
  • Anti-CD20 monoclonal antibody
  • An anthracycline-containing chemotherapy regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate renal, hepatic, pulmonary, and cardiac function

Who cannot join

  • Known CD19 negative or CD20 negative tumor
  • History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
  • Prior CAR therapy or other genetically modified T-cell therapy
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Prior CD19 targeted therapy
  • Clinically significant infection or cardiopulmonary disease
Show all 11Show fewer
  • Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
  • History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
  • History of autoimmune disease
  • History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • St. David's South Austin Medical Center

    Austin, Texas, 78704

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • City of Hope National Medical Center

    Duarte, California, 91010-3012

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Columbia University Medical Center, New York Presbyterian Hospital

    New York, New York, 10032

  • Stanford Cancer Institute

    Palo Alto, California, 94305

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • UCLA Hematology/Oncology

    Santa Monica, California, 90404

  • Swedish Cancer Institute

    Seattle, Washington, 98104

Other trials in United States

About this study

Official title: A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

Read the detailed description

Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

Being tested
Axicabtagene Ciloleucel, Rituximab, Fludarabine, Cyclophosphamide

What participants receive

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

  • Axicabtagene CiloleucelBiological

    Also called Yescarta®

    A single infusion of CAR-transduced autologous T cells administered intravenously

  • RituximabDrug

    Also called RITUXAN®

    Administered intravenously

  • FludarabineDrug

    Administered according to package insert

  • CyclophosphamideDrug

    Administered according to package insert

Study groups in NCT04002401
Study groupRoleWhat they receive
Axicabtagene Ciloleucel and Rituximab CombinationExperimentalParticipants will receive rituximab 375 mg/m^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m^2 over 30 minutes and cyclophosphamide 500 mg/m^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
Receives: Biological: Axicabtagene Ciloleucel; Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators

    CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR [complete metabolic response (CMR); complete radiological response (CRR)]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). 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; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.

    Measured: First infusion date up to maximum duration of 32.7 months

Secondary outcomes (10)

  1. Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

    An AE is defined as any untoward medical occurrence in a clinical trial participant that does not necessarily have a relationship with study treatment or worsening of a pre-existing medical condition. TEAEs are any AEs with onset on or after axicabtagene ciloleucel infusion or worsening of a pre-existing medical condition that occurs on or after axicabtagene ciloleucel infusion.

    Measured: First infusion date up to maximum duration of 27 months

  2. Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value

    Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Laboratory parameters with only non-zero values are presented.

    Measured: First infusion date up to maximum duration of 27 months

  3. Objective Response Rate (ORR) Per the IWG Lugano Classification as Determined by Study Investigators

    ORR: percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR); partial radiologic response (PRR)].CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in LDi;no extralymphatic sites of disease;absent NMLs;organ enlargement regress to normal;no new sites;bone marrow morphology normal. PMR: scores 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 (EOT). PRR: ≥ 50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by > 50% in length beyond normal; no new sites.

    Measured: First infusion date up to maximum duration of 32.7 months

  4. Duration of Response (DOR) Per the IWG Lugano Classification as Determined by Study Investigators

    DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression [progressive metabolic disease (PMD); progressive radiologic disease (PRD)] or death from any cause. Objective response is defined in outcome measure (OM) 4. PMD: scores 4 (uptake moderately > liver), 5 (uptake markedly > liver, new lesions) with increased uptake compared with baseline; new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma rather than another etiology; new or recurrent FDG-avid foci in bone marrow. PRD: LDi >1.5 cm; ≥ 50% increase from cross product of LDi and perpendicular diameter (PPD); increase in LDi or shortest axis perpendicular to the LDi (SDi) of 0.5 cm for lesions ≤1.5 cm and 1 cm for lesions >2 cm; spleen increased by >50% in length beyond normal; new or recurrent splenomegaly, bone marrow involvement; new lesions; progression of pre-existing lesions. Kaplan-Meier (KM) estimate of median was reported.

    Measured: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 32.7 months)

  5. Progression-Free Survival (PFS) Per the IWG Lugano Classification as Determined by Study Investigators

    PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression (PMD; PRD) or death from any cause. PMD: scores 4 (uptake moderately > liver), 5 (uptake markedly > liver, new lesions) with increased uptake compared with baseline; new FDG-avid foci consistent with lymphoma rather than another etiology; new or recurrent FDG-avid foci in bone marrow. PRD: LDi >1.5 cm; ≥ 50% increase from cross product of LDi and PPD; increase in LDi or SDi of 0.5 cm for lesions ≤1.5 cm and 1 cm for lesions >2 cm; spleen increased by >50% in length beyond normal; new or recurrent splenomegaly, bone marrow involvement; new lesions; progression of pre-existing lesions. KM estimate of median was reported.

    Measured: First infusion date up to disease progression or death regardless of cause (up to approximately 32.7 months)

  6. Overall Survival (OS)

    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause. KM estimate of median was reported.

    Measured: First infusion date up to death regardless of cause (up to approximately 32.7 months)

  7. Peak Level of Anti-CD19 CAR T Cells in Blood

    Peak was defined as the maximum number of CAR T cells in blood measured after infusion.

    Measured: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24

  8. Level of Anti-CD19 CAR T Cells in Blood by Visit

    Measured: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24

  9. Area Under the Curve of CAR T Cells From Day 0 to Day 28 (AUC0-28)

    AUC0-28 is defined as the area under curve in a plot of number of CAR T cells against scheduled visit from Day 0 to Day 28.

    Measured: Baseline (Day 0), post-infusion on Days 7, 14, 21, and 28

  10. Time to Peak Level of Anti-CD19 CAR T Cells in Blood

    Time to peak was defined as the number of days from the date of the axicabtagene ciloleucel infusion to the date of peak level defined as the maximum number of CAR T cells in blood measured after infusion.

    Measured: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24

Timeline

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

  1. First posted28 Jun 2019
  2. Study start5 Nov 2019
  3. Primary completion30 Jan 2023
  4. Study completion30 Jan 2023

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04002401
Sponsor's protocol ID
KT-US-471-0114
Other IDs
2019-004803-11, 2019
Acronym
ZUMA-14
Status last verified
Feb 2024
First submitted
27 Jun 2019
Last updated
20 Feb 2024
Data monitoring committee
No
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/

Publications

  • Strati P, Leslie L, Shiraz P, Budde LE, Oluwole OO, Ulrickson M, Ramakrishnan A, Zhang T, Sun J, Milletti F, Kanska J, Shen R, Neumann F, Xu H, Patel K. Axicabtagene ciloleucel in combination with rituximab for refractory large B cell lymphoma: the phase 2, single-arm ZUMA-14 trial. Nat Cancer. 2026 Feb;7(2):304-315. doi: 10.1038/s43018-025-01102-1. Epub 2026 Jan 5.

    PubMed 41492094

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PubMed 34515338

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axicabtagene Ciloleucel, Rituximab and Fludarabine in people with Refractory Large B-cell Lymphoma, run by Kite, A Gilead Company at 14 sites in United States.

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 11 inclusion and 11 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 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. 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 20 Feb 2024). 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?

Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators (time frame: First infusion date up to maximum duration of 32.7 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 NCT04002401, which also lists 2 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 20 Feb 2024.

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