A Study Evaluating the Safety and Effectiveness of Axicabtagene Ciloleucel in Subjects with Indolent Non-Hodgkin Lymphoma (iNHL) returning after, or resistant to, initial treatment.
- Conditions
- Relapsed or Refractory Indolent Non-Hodgkin Lymphoma (r/r) iNHL.MedDRA version: 20.0Level: PTClassification code 10065856Term: Non-Hodgkin's lymphoma unspecified histology indolentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001912-13-FR
- Lead Sponsor
- Kite Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 50
1. Active, histologically proven B-cell NHL that is generally regarded as indolent (eg FL, marginal zone lymphoma, lymphoplasmacytic lymphoma) that is also determined to be high risk as defined by one or more of the criteria below:
o Progression of B-cell iNHL within 24 months of original diagnosis of disease that was subsequently treated with first-line anti-CD20 monoclonal antibody- and cytotoxic agent-containing combination chemoimmunotherapy (eg, R-CHOP, R-Bendamustine, R-CVP, R-fludarabine).
Note: A biopsy of a progressing lesion is required prior to enrollment to show absence of transformation to diffuse large B-cell lymphoma (DLBCL) or other excluded histology (eg, FL Grade 3b)
o Progression of B-cell iNHL within 6 months of the completion of second- or greater-line therapy with anti-CD20 monoclonal antibody- and alkylating agent-containing chemoimmunotherapy (= 2 cycles)
o Progression of B-cell iNHL at any point following autologous transplantation
2. At least 1 measurable lesion according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
3. Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) lymphoma
4. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists).
5. Toxicities due to prior therapy must be stable and recovered to = Grade 1 (except for clinically non-significant toxicities, such as alopecia).
6. Age 18 or older
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Absolute neutrophil count (ANC) = 1000/uL
9. Platelet count = 75000/uL
10. Absolute lymphocyte count = 100/uL
11. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
o Creatinine clearance (as estimated by Cockcroft Gault) = 60 mL/min
o Serum ALT/AST = 2.5 upper limit of normal (ULN)
o Total bilirubin = 1.5 mg/dl, except in subjects with Gilbert’s syndrome
o Cardiac ejection fraction = 50% , no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
o No clinically significant pleural effusion
o Baseline oxygen saturation > 92% on room air
12. 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)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
1. Transformed FL
2. Small lymphocytic lymphoma
3. Histological Grade 3b FL
4. Known presence of lymphoma cells in the peripheral blood
5. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease-free and without anticancer therapy for at least 3 years
6. Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion
7. History of allogeneic stem cell transplantation
8. Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for retreatment
9. Prior CAR therapy or other genetically modified T-cell therapy
10. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
11. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management
12. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis (Hep) B or Hep C infection. Subjects with history of Hep B or Hep C infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.
13. Presence of lymphoma that is known to involve the full thickness of the gastric wall
14. 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.
15. Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid (CSF) malignant cells or brain metastases
16. 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
17. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
18. 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
19. Possible requirement for urgent therapy within 6 weeks after leukapheresis due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
20. History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus), resulting in end organ injury or requiring systemic immunosuppression or systemic disease modifying agents within the last 2 years. Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and subjects with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
21. History of deep vein thrombosis (DVT) or pulmonary embolism within 6 months of enrollment
22. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
23. History of severe immediate hypersensitivity reaction to any of the agents used in this study
24. Treatment with a live, attenuated vaccine within 6 weeks prior to the planned start of the conditioning regimen or anticipation of need for such a vaccine during the course of the study
25. Women of childbearing potential who are pregnant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method