Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Axicabtagene ciloleucel

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Participants 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.

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

Axicabtagene Ciloleucel

Kite Study Director

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.

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.

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

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)

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/

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.

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.

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

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.

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.

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.

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

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

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.

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.

Kite, A Gilead Company

All-cause mortality: All enrolled analysis set included all the enrolled participants.

Adverse events: Safety analysis set included all participants treated with any dose of axicabtagene ciloleucel.

Participants received rituximab 375 mg/m\^2 IV 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) administered IV once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10\^6 anti-CD19 CAR T cells/kg administered IV once on Day 0 and additional rituximab 375 mg/m\^2 of 5 doses, administered IV once every 28 days starting from Day 21 up to Day 133.

Axicabtagene Ciloleucel and Rituximab Combination

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

United States

Region of Enrollment

Safety analysis set included all participants treated with any dose of axicabtagene ciloleucel.

Medical Information

Modified intent-to-treat (mITT) analysis set included all enrolled participants who were treated with the target dose of axicabtagene ciloleucel and at least 1 dose of rituximab after axicabtagene ciloleucel infusion.

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

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

Alanine Aminotransferase

Aspartate Aminotransferase

Bilirubin

Calcium

Direct Bilirubin

Glucose

Magnesium

Urate

Participants in the safety analysis set were analyzed.

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

Participants in the mITT analysis set were analyzed.

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

Participants in the mITT analysis set with an objective response (CR+PR) were analyzed.

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

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

Overall Survival (OS)

Peak Level of Anti-CD19 CAR T Cells in Blood

Baseline (Day 0)

Day 7 Post-infusion

Day 14 Post-infusion

Day 21 Post-infusion

Day 28 Post-infusion

Day 49 Post-infusion

Day 105 Post-infusion

Day 180 Post-infusion

Month 9 Post-infusion

Month 12 Post-infusion

Month 15 Post-infusion

Month 18 Post-infusion

Month 24 Post-infusion

Participants in the safety analysis set with available data were analyzed.

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

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

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

Participants received rituximab 375 mg/m\^2 intravenously (IV) 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) administered IV 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 administered IV once on Day 0 and additional rituximab 375 mg/m\^2 of 5 doses, administered IV once every 28 days starting from Day 21 up to Day 133.

Spots Global Cancer Trial Database for Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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