A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE C19 in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL) (ZUMA-1)
- Conditions
- Non-Hodgkin Lymphoma (NHL)lymph node cancer10025322
- Registration Number
- NL-OMON54771
- Lead Sponsor
- Kite Pharma Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 50
101. Histologically confirmed aggressive B cell NHL, including the following
types defined by WHO 2008 (Campo 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 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,
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 investigators judgment, the subject is unlikely to complete all
protocol-required study v
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1 Study:<br /><br>- Incidence of adverse events defined as dose-limiting toxicities (DLT)<br /><br><br /><br>Phase 2 Pivotal Study:<br /><br>Objective response rate (complete response [CR] + partial response [PR]) per<br /><br>the revised International Working Group (IWG) Response Criteria for Malignant<br /><br>Lymphoma (Cheson et al, 2007) as determined by study investigators. All<br /><br>subjects who do not meet the criteria for an objective response by the analysis<br /><br>cutoff date will be considered non-responders.<br /><br><br /><br>Phase 2 Safety Management Study:<br /><br>Incidence and severity of CRS and neurologic toxicities.</p><br>
- Secondary Outcome Measures
Name Time Method