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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03761056




Registration number
NCT03761056
Ethics application status
Date submitted
29/11/2018
Date registered
3/12/2018
Date last updated
2/11/2023

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Scientific title
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)
Secondary ID [1] 0 0
2019-002291-13
Secondary ID [2] 0 0
KTE-C19-112
Universal Trial Number (UTN)
Trial acronym
ZUMA-12
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Axicabtagene Ciloleucel
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cyclophosphamide

Experimental: Axicabtagene Ciloleucel - 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.


Treatment: Other: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Treatment: Drugs: Fludarabine
Administered according to package insert

Treatment: Drugs: Cyclophosphamide
Administered according to package insert
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
Timepoint [1] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (maximum duration: 26.2 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators
Timepoint [1] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (maximum duration: 26.2 months)
Secondary outcome [2] 0 0
Duration of Response (DOR) Per the Lugano Classification
Timepoint [2] 0 0
From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 26.2 months)
Secondary outcome [3] 0 0
Event-Free Survival (EFS)
Timepoint [3] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [6] 0 0
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Serious Adverse Events (SAE)
Timepoint [6] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [7] 0 0
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value
Timepoint [7] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [8] 0 0
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value
Timepoint [8] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [9] 0 0
Relapse With Central Nervous Disease (CNS) Disease
Timepoint [9] 0 0
First infusion date of axicabtagene ciloleucel to data cut off date of 17 May 2021 (Up to approximately 26.2 months)
Secondary outcome [10] 0 0
Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood
Timepoint [10] 0 0
From enrollment up to Month 24
Secondary outcome [11] 0 0
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8
Timepoint [11] 0 0
From enrollment up to Week 4
Secondary outcome [12] 0 0
Peak Serum Level of C-Reactive Protein (CRP)
Timepoint [12] 0 0
From enrollment up to Week 4
Secondary outcome [13] 0 0
Peak Serum Level of Ferritin
Timepoint [13] 0 0
From enrollment up to Week 4
Secondary outcome [14] 0 0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin
Timepoint [14] 0 0
From enrollment up to Week 4

Eligibility
Key inclusion criteria
Key

* Histologically confirmed large B-cell lymphoma
* High-grade large B-cell lymphoma
* Individuals must have a positive interim positron emission tomography (PET) per Cheson, 2014 (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

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/10/2023
Sample size
Target
Accrual to date
Final
42
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
France
State/province [6] 0 0
Paris

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kite, A Gilead Company
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT03761056
Trial related presentations / publications
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.
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.
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).
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.
Public notes

Contacts
Principal investigator
Name 0 0
Kite Study Director
Address 0 0
Kite, A Gilead Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03761056