A Study Evaluating the Efficacy of KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL)
- Conditions
- Relapsed/Refractory Mantle Cell Lymphoma (MCL)MedDRA version: 20.0Level: PTClassification code 10061275Term: Mantle cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005008-27-DE
- Lead Sponsor
- Kite Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
101. Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
102. Up to 5 prior regimens for MCL.
Cohort 1 and Cohort 2: Prior therapy must have included:
- Anthracycline or bendamustine-containing chemotherapy and
- Anti-CD20 monoclonal antibody therapy and
- Ibrutinib or acalabrutinib
Cohort 3: Prior therapy must have included anthracycline- or bendamustine or high-dose cytarabine containing chemotherapy and anti-CD20 monoclonal antibody therapy. Subjects in
Cohort 3 must not have received prior therapy with a BTKi.
103. Relapsed or refractory disease, as defined by the following:
- Disease progression after last regimen, or
- Failure to achieve a PR or CR to the last regimen
104. At least 1 measurable lesion. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. If the only measurable disease is lymph node disease, at least one lymph node should be = 2 cm
105. For subjects in Cohort 1 and Cohort 2 only: 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 or BTKi (ibrutinib or acalabrutinib; as applicable for subjects in Cohort 1 and Cohort 2) 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 years or older
109. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
110. ANC = 1000/uL
111. Platelet count = 75,000/µL. For subjects in Cohort 3 with bone marrow involvement, platelet count = 50,000/µL is acceptable.
112. Absolute lymphocyte count = 100/ µL
113. Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) = 60 cc/min
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 2.5 upper limit of normal (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 echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings. For subjects in Cohort 3, a multigated acquisition (MUGA) scan may be used in place of ECHO.
- No clinically significant pleural effusion for subjects in Cohort 1 and Cohort 2, and no clinically significant pleural effusion, pericardial effusion, or ascites for subjects in Cohort 3
- Baseline oxygen saturation > 92% on room air
114. 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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
201. History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
202. Autologous stem cell transplant within 6 weeks of planned KTE-X19 or axicabtagene ciloleucel infusion.
203. History of alloSCT, with the exception of subjects in Cohort 3 with no donor cells detected on chimerism > 100 days after alloSCT
204. Prior CD19 targeted therapy with the exception of subjects who received KTE-X19 or axicabtagene ciloleucel in this study and are eligible for retreatment.
205. Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
206. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
207. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite Medical Monitor.
208. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Subjects with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing. For subjects in Cohort 3 enrolled in France, those with any history of acute or chronic hepatitis B or C infection are excluded.
209. Presence of any indwelling line or drain (e.g. percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
210. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
211. History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease,
cerebral edema, posterior reversible encephalopathy syndrome (PRES), or any autoimmune disease with CNS involvement
212. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmias, or other clinically significant cardiac disease within 12 months of enrollment
213. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
214. History of deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of enrollment
215. Possible requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis
syndrome)
216. Primary immunodeficiency
217. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
218. History of severe immediate hypersensitivity reaction to any of the agents used in this study
219. Live vaccine = 6 weeks prior to planned start of conditioning regimen
220. Females of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant
221. Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of KTE-X19 or axicabtagene ciloleucel infusion
222. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow
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