Clinical trial NCT03153462: Axicabtagene Ciloleucel Expanded Access Study
Official title: A Multicenter, Open-label, Expanded Access Study of Axicabtagene Ciloleucel for the Treatment of Subjects With Relapsed/Refractory Large B-cell Lymphoma.
Study type: EXPANDED_ACCESS
Overall status: APPROVED_FOR_MARKETING
Conditions: Relapsed/Refractory Diffuse Large B Cell Lymphoma
Relapsed/Refractory Primary Mediastinal B Cell Lymphoma
Relapsed/Refractory Transformed Follicular Lymphoma
Relapsed/Refractory High-Grade B-Cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-05-15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT

Brief summary: A multicenter, open-label expanded access protocol for the treatment of subjects with relapsed/refractory large B-cell lymphoma.

Subjects 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: Inclusion Criteria:

1. Histologically confirmed large B-cell lymphoma, including the following types:

   1. DLBCL, not otherwise specified
   2. Primary mediastinal large B-cell lymphoma
   3. High-grade B-cell lymphoma
   4. DLBCL arising from follicular lymphoma (transformed follicular lymphoma, or TFL)
2. Relapsed or refractory disease, defined as one or more of the following:

   1. No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line therapy chemotherapy are excluded OR
   2. No response or relapse to second or greater lines of therapy OR
   3. Relapsed after ASCT
3. Subjects must have received adequate prior therapy including at a minimum:

   1. anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
   2. an anthracycline containing chemotherapy regimen;
4. No evidence, suspicion, and/or history of central nervous system (CNS) involvement of lymphoma
5. Age 18 or older
6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
7. Absolute neutrophil count ANC ≥1000/μL
8. Platelet count ≥75,000/μL
9. Absolute lymphocyte count ≥100/μL
10. Adequate renal, hepatic, pulmonary and cardiac function defined as:

    1. Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
    2. Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤2.5 upper limit of normal (ULN)
    3. Total bilirubin ≤1.5 mg/dL, except in subjects with Gilbert's syndrome.
    4. Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion within 180 days provide the subject did not receive an anthracycline based treatment or experience a cardiac event or change in performance status
    5. No clinically significant pleural effusion
    6. Baseline oxygen saturation \>92% on room air
11. Cohort 2 inclusion criteria: Subjects whose commercial manufacture of axicabtagene ciloleucel did not meet commercial release specification(s)

Exclusion Criteria:

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
2. History of allogeneic stem cell transplantation (SCT)
3. Prior CD19 targeted therapy
4. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
5. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
6. Presence or suspicion 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 and after consultation with the Kite Pharma Medical Monitor
7. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or hepatitis C infection. Subjects with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
8. History or presence of primary CNS lymphoma and/or CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
9. Cohort 2 exclusion criteria: Any medical condition that, deemed by the investigator, may interfere with assessment of safety or efficacy of study treatment

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer and Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Westwood
country: United States
facility: The University of Kansas Hospital Investigational Drug Services
state: Kansas
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: