A phase 3 study to assess the efficacy and safety of JCAR017, a CAR-T cell therapy, in adults with aggressive B-Cell non-Hodgkin lymphoma
- Conditions
- Transplant-eligible relapsed or refractory (R/R) aggressive B-cell Non Hodgkin Lymphoma (B-NHL)MedDRA version: 23.0Level: LLTClassification code 10029593Term: Non-Hodgkin's lymphoma NOSSystem Organ Class: 100000004864MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-000929-32-IT
- Lead Sponsor
- CELGENE CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 182
1. Subject is at least 18 years and no older than 75 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. ECOG performance status less than or equal to 1.
5. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed FL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triplehit lymphoma [DHL/THL]) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology. If archival sample is before most recent relapse or no or insufficient archival sample is available, a new tumor biopsy is mandated to confirm
diagnosis. Note: Subjects with secondary CNS involvement are eligible.
Selection of subjects should take into account clinical risk factors for serious adverse events (EAs) and alternative treatment options. Subjects should only be enrolled if the Investigator decides that the potential benefit outweighs the risk to the subjects.
6. Refractory (SD, PD, PR or CR with relapse before 3 months) or relapsed (CR with relapse on or after 3 months) within 12 months from CD20 antibody and anthracycline containing first line therapy.
7. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening.
8. Adequate organ function, defined as:
- Adequate bone marrow function as assessed by the Investigator
- Serum creatinine < 1.5 x age-adjusted upper limit of normal (ULN) or creatinine clearance > 30 mL/min (estimated glomerular filtration rate [eGFR] by Cockcroft Gault see Appendix D for calculation)
- Alanine aminotransferase (ALT) less than or equal to 5 x ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver)
- Adequate pulmonary function, defined as less than or equal to Grade 1 dyspnea according to Common Terminology Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) greater than or equal to 92% on room air and FEV^1 greater than or equal to 50%.
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) greater than or equal to 40% as assessed by echocardiogram (ECHO) or multi-gated
acquisition scan (MUGA) performed within 4 weeks of randomization
9. Adequate vascular access for leukapheresis
10. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals while receiving as well as within 12 months after the JCAR017 infusion and until CAR T cells are no longer present by quantitative polymerase chain reaction (qPCR) on 2
consecutive tests, whichever occurs last.
For following criteria please kindly refer to protocol.
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 91
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 91
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in
the study.
2. Subject has any condition including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if participating in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
5. Subjects planned to undergo allogeneic stem cell transplantation.
6. Subjects with primary large B cell cutaneous lymphoma, DLBCL positive for EBV (Epstein-Barr virus) of the elderly and Burkitt lymphoma.
7. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for at least 2 years with the exception of the following noninvasive malignancies:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
- Other completely resected stage 1 solid tumor with low risk for recurrence
8. Treatment with any prior gene therapy product
9. Subjects who have received previous CD19-targeted therapy.
10. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
11. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other
treatment.
12. Active autoimmune disease requiring immunosuppressive therapy.
13. History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac
angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
14. History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
15.Tumor infiltration of the venous or arterial vessels.
For following criteria please kindly refer to protocol.
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