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

B-cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Axicabtagene ciloleucel

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Axicabtagene Ciloleucel

Kite Study Director

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

After the end of KTE-C19-112 (ZUMA-12), participants who received an infusion of axicabtagene ciloleucel will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.

Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma

A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12)

Complete Response Rate (CRR): 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.

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 after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause. Objective response is defined in outcome measure (OM) 2.

EFS was defined as time from axicabtagene ciloleucel infusion date to earliest date of disease progression (Lugano classification), commencement of subsequent new anti-lymphoma therapy including stem cell transplant, or death from any cause.

PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause.

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause.

An AE was any untoward medical occurrence in a participant in a clinical trial participant, which did not necessarily have a causal relationship with the treatment. Treatment-emergent adverse events were defined as any adverse event with onset on or after the axicabtagene ciloleucel infusion. Serious adverse event was defined as an event that resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; and medically important event or reaction.

Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Grading categories were determined by CTCAE version 5.0.

Relapse with CNS disease was defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of CNS involvement with lymphoma as determined by typical symptoms, cerebrospinal fluid (CSF) evaluation, and/or diagnostic imaging.

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

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Time to peak is defined as the number of days from axicabtagene ciloleucel infusion to the date when the cytokine first reached the maximum post-baseline level.

Kite, A Gilead Company

All-Cause Mortality: All Enrolled Analysis Set included all enrolled/leukapheresed participants.

Adverse Events: For Axicabtagene Ciloleucel arm: Safety Analysis Set included all participants treated with any does of axicabtagene ciloleucel.

For Retreatment arm: Safety Retreatment Analysis Set consisted of all participants who underwent retreatment with axicabtagene ciloleucel.

Participants received 500 mg/m\^2 cyclophosphamide IV and 30 mg/m\^2/day fludarabine IV conditioning chemotherapy followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered.

This arm included participants who achieved partial response or complete response and subsequently experienced disease progression and received second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

Retreatment Axicabtagene Ciloleucel

Participants received cyclophosphamide 500 mg/m\^2/day IV and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

United States

France

Australia

Region of Enrollment

Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel.

Medical Information

The response evaluable analysis set included participants who were enrolled and treated with axicabtagene ciloleucel at a dose of at least 1 x 10\^6 anti-CD19 CAR T cells/kg, and centrally confirmed disease type (double-/triple- hit lymphomas) or International Prognostic Index (IPI) score ≥ 3.

Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators

Participants in Response Evaluable Analysis Set were analyzed.

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

Participants in Response Evaluable Analysis Set were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date or new anti-lymphoma therapy start (including stem cell transplant or retreatment of axicabtagene ciloleucel), whichever is earlier.

Duration of Response (DOR) Per the Lugano Classification

Participants in Response Evaluable Analysis Set were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date.

Event-Free Survival (EFS)

Participants received cyclophosphamide 500 mg/m\^2 IV and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered.

Participants in Response Evaluable Analysis Set were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cut off date or new antilymphoma therapy start date (including stem cell transplant or retreatment of axicabtagene ciloleucel) whichever is earlier.

Progression-Free Survival (PFS)

Participants in Response Evaluable Analysis Set were analyzed. Participants who have not died by the analysis data cutoff date were censored at their last known alive date prior to the data cutoff date with the exception that the participants known to be alive or determined to have died after the data cutoff date were censored at the data cuttoff date.

Overall Survival (OS)

TEAE

Treatment-Emergent SAE

For Axicabtagene Ciloleucel arm: Safety Analysis Set included all participants treated with any does of axicabtagene ciloleucel.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Serious Adverse Events (SAE)

Hemoglobin

Alanine Aminotransferase

Alkaline Aminotransferase

Aspartate Aminotransferase

Bilirubin

Calcium

Creatinine

Glucose

Magnesium

Sodium

Urate

Participants in Safety Analysis Set were analyzed.

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

Leukocytes

Lymphocytes

Neutrophils

Platelets

Albumin

Potassium

Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value

Participants in response evaluable analysis set with available data were analyzed.

Relapse With Central Nervous Disease (CNS) Disease

Participants in safety analysis set were analyzed.

Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood

Granzyme B

IFNg

IL-2

IL-5

IL-6

IL-8

Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8

Peak Serum Level of C-Reactive Protein (CRP)

Peak Serum Level of Ferritin

Ferritin

Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin

Participants received cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered.

Spots Global Cancer Trial Database for Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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