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

Overview

About this study

The purpose of this study is to determine if axicabtagene ciloleucel is superior to standard of care (SOC) as measured by event-free survival (EFS), as determined by blinded central review.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al., 2016):
    • DLBCL not otherwise specified (including ABC/GCB);
    • HGBL with or without MYC and BCL2 and/or BCL6 rearrangement;
    • DLBCL arising from FL o T-cell/histiocyte rich large B-cell lymphoma;
    • DLBCL associated with chronic inflammation;
    • Primary cutaneous DLBCL, leg type;
    • Epstein-Barr virus (EBV) + DLBCL.
  • Relapsed or refractory disease after first-line chemoimmunotherapy:
    • Refractory disease 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 (e.g., 4 cycles of R-CHOP);
    • PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy.
  • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse ≤ 12 months of first-line therapy.
  • 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.
  • Intent to proceed to HDT and ASCT if response to second-line therapy.
  • Subjects must have radiographically documented disease.
  • No known history or suspicion of central nervous system (CNS) involvement by lymphoma.
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent.
  • Age 18 years or older at the time of informed consent.
  • ECOG performance status of 0 or 1.
  • Adequate bone marrow, renal, hepatic, pulmonary and cardiac function defined as:
    • Absolute neutrophil count (ANC) ≥1000/μL;
    • Platelet count ≥ 75,000/μL;
    • Absolute lymphocyte count ≥ 100/μL;
    • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min;
    • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN);
    • Total bilirubin ≤ 1.5 mg/dl, except in subjects 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.
  • Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).

Exclusion Criteria:

  • 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.
  • History of Richter’s transformation of CLL or PMBCL.
  • History of autologous or allogeneic stem cell transplant.
  • Received more than one line of therapy for DLBCL.
  • Prior CD19 targeted therapy.
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel or SOC.
  • Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy or prior randomization into ZUMA-7.
  • History of severe, immediate hypersensitivity reaction attributed to aminoglycosides.
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
  • 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.
  • Active tuberculosis.
  • Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
  • Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases.
  • 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.
  • Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
  • 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 disease within 12 months of enrollment.
  • Requirement for urgent therapy due to tumor mass effects, such as bowel obstruction or blood vessel compression.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Patrick Johnston, M.D., Ph.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Januario Castro, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms. Read More on PubMed
  • The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20409731

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