ZUMA Trial

This is a phase 3, randomized, open-label study evaluating the efficacy of axicabtagene ciloleucel versus standard-of-care therapy in subjects with relapsed/refractory diffuse large B-cell lymphoma.

The blood and marrow transplant and cellular therapeutics team at The University of Kansas Cancer Center is excited to begin enrolling patients in a new clinical trial that will make revolutionary CAR T-cell therapy available to eligible patients as a second-line therapy for relapsed/refractory diffuse large B-cell lymphoma.

To be considered for the ZUMA-7 clinical trial, it is critical that patients MUST NOT have begun receiving second-line salvage chemotherapy.

Study details and eligibility criteria follow. For an assessment of a patient’s eligibility for enrollment, please contact our BMT/CAR T nurse navigator at 913-588-9187 or hematology_navigation@kumc.edu. Our toll-free number is 1-844-323-1227. International callers may dial 00-1-913-588-1227.

ZUMA-7 (NCT03391466)
This is an important phase 3 global study for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the second-line setting, comparing CAR T-cell therapy head-to-head with standard-of-care second-line therapy: salvage chemotherapy (e.g., R-ICE) and if in response, high-dose therapy + autologous stem cell transplant.

In the ZUMA-7 study, the patient population includes adults with primary refractory and early-relapsed DLBCL after first-line chemotherapy (e.g., R-CHOP). Early relapsers are defined as those who achieve complete remission but relapse within 12 months of initiation of first-line chemotherapy. Patients will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel (axi-cel) or standard-of-care second-line therapy.

We appreciate your assistance with recruitment efforts for ZUMA-7 and believe this research may be of interest to you and to your patients. The results may be practice-changing in a patient population with significant unmet need. Patients must be considered for ZUMA-7 PRIOR TO initiating second-line salvage chemotherapy.

About the study drug
Axi-cel has been approved by the FDA for use in adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Axi-cel treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously.

Study objectives
The primary objective is to determine if axi-cel therapy improves the clinical outcome compared with standard-of-care second-line therapy in patients with relapsed/refractory DLBCL. Key secondary endpoints will be objective response rate (ORR) and overall survival (OS); additional secondary objectives will include additional safety, efficacy and quality-of-life endpoints.

Study design
Approximately 350 patients will be randomized to either the axi-cel arm or the standard-of-care arm in a 1:1 ratio.

Your patients may be eligible to participate if they are ≥ 18 years and if they meet the following basic inclusion and exclusion 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
• Refractory disease is defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded.

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 (e.g., 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.

We invite you to refer any patients with large B-cell lymphoma who may be eligible for ZUMA-7 with primary refractory disease or early relapsers at the time of first relapse PRIOR TO starting salvage chemotherapy. All interested patients will be assessed in detail for eligibility. After the completion of the study, your patient will return to your full care, and their case notes can be shared with you upon request.