A Study Evaluating the Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma

The purpose of this study is to evaluate whether axicabtagene ciloleucel therapy improves the
clinical outcome compared with standard of care second-line therapy in patients with
relapsed/refractory DLBCL.

Eligibility Criteria

Key Inclusion Criteria:

1. Histologically proven DLBCL, including transformation from follicular lymphoma

2. Relapsed or refractory disease after first-line chemoimmunotherapy

- Refractory disease is defined as no complete remission to first-line therapy;
subjects who are intolerant to first-line therapy are excluded.

- Progressive disease (PD) as best response to first-line therapy

- Stable disease (SD) as best response after at least 4 cycles of first-line
therapy

- Partial response (PR) as best response after at least 6 cycles and
biopsy-proven residual disease or disease progression ≤ 12 months from
initiation of therapy

- Relapsed disease defined as complete remission to first-line therapy followed by
biopsy-proven relapse ≤ 12 months of initiating first-line therapy

3. Subjects must have received adequate first-line therapy including at a minimum:

- Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20
negative, and

- An anthracycline containing chemotherapy regimen

4. No known history or suspicion of central nervous system involvement by lymphoma

5. ECOG performance status of 0 or 1

6. Adequate bone marrow function as evidenced by:

- ANC ≥ 1000/uL

- Platelet ≥ 75,000/uL

- Absolute lymphocyte count ≥ 100/uL

7. Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

- Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min

- Serum ALT/AST ≤ 2.5 ULN

- Total bilirubin ≤ 1.5 mg/dl

- Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as
determined by an ECHO, and no clinically significant ECG findings

- No clinically significant pleural effusion

- Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg
cervix, bladder, breast) unless disease free for at least 3 years

2. Received more than one line of therapy for DLBCL

3. History of autologous or allogeneic stem cell transplant

4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
requiring intravenous antimicrobials for management.

5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B
(HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive
history of treated hepatitis B or hepatitis C, the viral load must be undetectable per
quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.

6. Subjects with detectable cerebrospinal fluid malignant cells or known brain
metastases, or with a history of cerebrospinal fluid malignant cells or brain
metastases.

7. History or presence of non-malignant CNS disorder such as seizure disorder,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune
disease with CNS involvement

8. Presence of any indwelling line or drain. Dedicated central venous access catheter
such as a Port-a-Cath or Hickman catheter are permitted.

9. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina,
New York Heart Association Class II or greater congestive heart failure, or other
clinically significant cardiac diseases within 12 months of enrollment

10. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of
enrollment

11. History of autoimmune disease, requiring systemic immunosuppression and/or systemic
disease modifying agents within the last 2 years

12. History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7

Principal Investigator

Joseph McGuirk, DO

Study Contact

William Wesson, wwesson@kumc.edu, (913) 588-5565

Estimated Completion Date

Saturday, January 15, 2022

ClinicalTrials.gov #

NCT03391466
06/11/2018