NCT03761056

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jan 2019

Longer than P75 for phase_2

Geographic Reach
3 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 29, 2018

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 3, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

January 29, 2019

Completed
3.4 years until next milestone

Results Posted

Study results publicly available

July 8, 2022

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 12, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 12, 2023

Completed
Last Updated

December 4, 2024

Status Verified

November 1, 2024

Enrollment Period

4.7 years

First QC Date

November 29, 2018

Results QC Date

May 16, 2022

Last Update Submit

November 13, 2024

Conditions

B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

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

    CR Rate is the 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.

    Up to 4 years

Secondary Outcomes (14)

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

    Up to 4 years

  • Duration of Response (DOR) Per the Lugano Classification

    Up to 4 years

  • Event-Free Survival (EFS)

    Up to 4 years

  • Progression-Free Survival (PFS)

    Up to 4 years

  • Overall Survival (OS)

    Up to 4 years

  • +9 more secondary outcomes

Study Arms (1)

Axicabtagene Ciloleucel

EXPERIMENTAL

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. Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.

Biological: Axicabtagene CiloleucelDrug: FludarabineDrug: Cyclophosphamide

Interventions

Axicabtagene CiloleucelBIOLOGICAL

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

Also known as: Yescarta®
Axicabtagene Ciloleucel
FludarabineDRUG

Administered according to package insert

Axicabtagene Ciloleucel
CyclophosphamideDRUG

Administered according to package insert

Axicabtagene Ciloleucel

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed large B-cell lymphoma
  • High-grade large B-cell lymphoma
  • Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
  • No evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count ≥ 1000/μL
  • Platelet count ≥ 75,000/μL
  • Absolute lymphocyte count ≥ 100/μL
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as:
  • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN)
  • Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
  • No clinically significant pleural effusion
  • Baseline oxygen saturation \> 92% on room air

You may not qualify if:

  • History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
  • History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
  • History of autologous or allogeneic stem cell transplant
  • Prior CD19-targeted therapy
  • Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
  • Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
  • History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
  • Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
  • Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma
  • History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  • History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Banner Health MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope

Duarte, California, 91010-3012, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Hopital Saint Louis

Paris, 75475, France

Location

Related Publications (6)

  • Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, et al. 739 Primary Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 63rd American Society of Hematology (ASH) Annual Meeting and Exposition; 2021 11-14 December.

    BACKGROUND

  • Neelapu SS, Dickinson M, Ulrickson ML, Oluwole OO, Herrera AF, Thieblemont C, et al. 405 Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 62nd American Society of Hematology (ASH) Annual Meeting and Exposition Virtual; 2020 05-08 December.

    BACKGROUND

  • Neelapu SS, Chavez JC, Lin Y, Munoz J, Ujjani CS, Riedell P, et al. ZUMA-12: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) as a First-Line Therapy in Patients (Pts) with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. J Clin Oncol 2019;37 (15).

    BACKGROUND

  • Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, Herrera AF, Ujjani CS, Lin Y, Riedell PA, Kekre N, de Vos S, Lui C, Milletti F, Dong J, Xu H, Chavez JC. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022 Apr;28(4):735-742. doi: 10.1038/s41591-022-01731-4. Epub 2022 Mar 21.

    PMID: 35314842BACKGROUND

  • Chavez JC, Dickinson M, Munoz JL, Ulrickson ML, Thieblemont C, Oluwole OO, et al. 3-Year Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL). Blood 2023;142 (Supplement 1):894-7

    BACKGROUND

  • Chavez JC, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, Herrera AF, Ujjani CS, Lin Y, Riedell PA, Kekre N, de Vos S, Wulff J, Williams CM, Winters J, Kloos I, Xu H, Neelapu SS. Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study. Blood. 2025 May 15;145(20):2303-2311. doi: 10.1182/blood.2024027347.

    PMID: 39938019DERIVED

Related Links

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

axicabtagene ciloleucelfludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Results Point of Contact

Title
Medical Information
Organization
Kite, A Gilead Company
medinfo@kitepharma.com
844-454-5483 (1-844-454-KITE)

Study Officials

  • Kite Study Director

    Kite, A Gilead Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 29, 2018

First Posted

December 3, 2018

Study Start

January 29, 2019

Primary Completion

October 12, 2023

Study Completion

October 12, 2023

Last Updated

December 4, 2024

Results First Posted

July 8, 2022

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)US(5)AU(1)