A Study Evaluating the Safety and Effectiveness of KTE C19 in Subjects with Aggressive Non-Hodgkin Lymphoma (NHL) resistant to other treatments.
- Conditions
- Diffuse Large B-cell Lymphoma (DLBCL), Primary Mediastinal B cell lymphoma (PMBCL) and Transformed Follicular Lymphoma (TFL).MedDRA version: 20.0Level: HLTClassification code 10036711Term: Primary mediastinal large B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005007-86-DE
- Lead Sponsor
- Kite Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 286
101. Histologically confirmed aggressive B cell NHL, including the following types defined by WHO 2008 (Campo et al, 2011):
- DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV)+ DLBCL of the elderly; OR
- primary mediastinal (thymic) large B cell lymphoma
- transformation of follicular lymphoma to DLBCL will also be included
102. Chemotherapy-refractory disease, defined as one or more of the following:
- No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line therapy chemotherapy are excluded
- PD as best response to first-line therapy
- SD as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy
OR
- No response to second or greater lines of therapy
- PD as best response to most recent therapy regimen
- SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy
OR
- Refractory post-ASCT
- Disease progression or relapsed =12 months of ASCT (must have biopsy proven recurrence in relapsed subjects)
- if salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy
103. Subjects must have received adequate prior therapy including at a minimum:
- anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
- an anthracycline containing chemotherapy regimen;
- for subjects with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL
104. At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
105. MRI of the brain showing no evidence of CNS lymphoma
106. 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 (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists etc).
107. Toxicities due to prior therapy must be stable and recovered to = Grade 1 (except for clinically non-significant toxicities such as alopecia)
108. Age 18 or older
109. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
110. ANC =1000/uL
111. Platelet count =75,000/uL
112. Absolute lymphocyte count =100/uL
113. Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) = 60 mL/min
- Serum ALT/AST =2.5 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 ECHO, and no clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline oxygen saturation >92% on room air
114. Females of childbe
201. 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
202. History of Richter’s transformation of CLL
203. Autologous stem cell transplant with therapeutic intent within 6 weeks of planned axicabtagene ciloleucel infusion
204. History of allogeneic stem cell transplantation
205. Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment
206. Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
207. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
208. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
209. History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with 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 or
applicable country guidelines.
210. Presence of any indwelling line or drain (e.g., 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
211. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
212. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
213. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
214. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
215. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
216. Primary immunodeficiency
217. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment
218. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
219. History of severe immediate hypersensitivity reaction to any of the agents used in this study
220. Live vaccine = 6 weeks prior to planned start of conditioning regimen
221. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
222. Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of conditioning therapy.
223. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
224. History of au
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