Clinical trial NCT03761056: Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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

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.

Primary outcomes:
measure: Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
timeFrame: Up to 4 years
Secondary outcomes:
measure: Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators
timeFrame: Up to 4 years
measure: Duration of Response (DOR) Per the Lugano Classification
timeFrame: Up to 4 years
measure: Event-Free Survival (EFS)
timeFrame: Up to 4 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE)
timeFrame: Up to 2 years
measure: Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value
timeFrame: Up to 2 years
measure: Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value
timeFrame: Up to 2 years
measure: Relapse With Central Nervous System (CNS) Disease
timeFrame: Up to 4 years
measure: Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood
timeFrame: Up to Month 24
measure: Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8
timeFrame: Up to Week 4
measure: Peak Serum Level of C-Reactive Protein (CRP)
timeFrame: Up to Week 4
measure: Peak Serum Level of Ferritin
timeFrame: Up to Week 4
measure: Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin
timeFrame: Up to Week 4
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Paris
country: France
facility: Hopital Saint Louis
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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).
citation: 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.
citation: 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