Phase 2
Completed N=42
Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Source: ClinicalTrials.gov NCT03761056 ↗Enrolled (actual)
42
Serious AEs
56.1%
Results posted
Jul 2022
Primary outcomePrimary: Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators — 86 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators |
86 | — |
| SECONDARY Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators |
92 | — |
| SECONDARY Duration of Response (DOR) Per the Lugano Classification |
NA | — |
| SECONDARY Event-Free Survival (EFS) |
NA | — |
| SECONDARY Progression-Free Survival (PFS) |
NA | — |
| SECONDARY Overall Survival (OS) |
NA | — |
| SECONDARY Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE) |
100; 55 | — |
| SECONDARY Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value |
3; 8; 0; 5; 20; 5 | — |
| SECONDARY Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value |
43; 93; 75; 95; 25; 3 | — |
| SECONDARY Relapse With Central Nervous System (CNS) Disease |
— | — |
| SECONDARY Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood |
36.27 | — |
| SECONDARY Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 |
28.5; 409.4; 16.4; 6.3; 35.1; 63.0 | — |
| SECONDARY Peak Serum Level of C-Reactive Protein (CRP) |
208.4 | — |
| SECONDARY Peak Serum Level of Ferritin |
749.1 | — |
| SECONDARY Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin |
8; 4; 4; 1; 8; 8 | — |
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.
Data sourced from ClinicalTrials.gov (NCT03761056). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.