A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-C19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL)
The goal of this clinical research study is to learn if KTE-C19 can help to control relapsed/refractory MCL when given after a 3-day course of chemotherapy. The safety of the drug will also be studied.
Disease Group: Lymphoma
Treatment Agent: KTE-C19
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Kite Pharma, Inc.
The primary objective is to evaluate the efficacy of KTE-C19, as measured by objective response rate, in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL). Secondary objectives will include assessing the safety and tolerability of KTE-C19 and additional efficacy endpoints. The study will also assess the change in European Quality of Life-5 Dimensions (EQ-5D) scores from baseline to Month 6.
IRB Review and Approval Date: 12/18/2015
Recruitment Status: Open
Projected Accrual: 80
1) Pathologically confirmed MCL, with documentation of either
overexpression of cyclin D1 or presence of t(11;14)
2) Up to 5 prior regimens for MCL. Prior therapy must have included: *Anthracycline or bendamustine-containing chemotherapy and * Anti-CD20 monoclonal antibody therapy and * Ibrutinib or acalabrutinib
3) Relapsed or refractory disease, defined by the following: * Disease progression after last regimen, or * Refractory disease is defined failure to achieve a PR or CR to the last regimen
4) At least 1 measurable lesion according to the revised International Working. Group (IWG) Response Criteria for Malignant Lymphoma. 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
5) MRI of the brain showing no evidence of CNS lymphoma
6) At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior radiation therapy or systemic therapy at the time the subject is planned for leukapheresis
7) Toxicities due to prior therapy must be stable or recovered to </= Grade 1 (except for clinically non-significant toxicities such as alopecia)
8) Age 18 years or older
9) Eastern cooperative oncology group (ECOG) performance status of 0 or 1
10) Absolute neutrophil count (ANC) >/= 1000/uL
11) Platelet count >/= 75,000/uL
12) Absolute lymphocyte count >/= 100/ uL
13) Adequate renal, hepatic, pulmonary and cardiac function defined as: * Creatinine clearance (as estimated by Cockcroft Gault) >/= 60 cc/min; * Serum creatinine </= 1.5 mg/dl * Serum aspartate transaminase (AST)/alanine transaminase (ALT) </= 2.5 upper limit of normal (ULN) * Total bilirubin </= 1.5 mg/dl, except in subjects with Gilbert’s syndrome. * Cardiac ejection fraction >/= 50% [by echocardiogram (ECHO)] and no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings; * No clinical significant pleural effusion; * Baseline oxygen saturation > 92% on room air.
14) 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
1) 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
2) Autologous stem cell transplant within 6 weeks of planned KTE-C19 infusion
3) History of allogeneic stem cell transplantation
4) Prior CD19 targeted therapy with the exception of subjects who received KTE-C19 in this study and are eligible for re-treatment
5) Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
6) History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
7) 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
8) History of 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.
9) 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
10) Subjects with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of CNS lymphoma,cerebrospinal fluid malignant cells or brain metastases
11) 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
12) History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
13) Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
14) History of symptomatic deep vein thrombosis or pulmonary embolism within the last 6 months of enrollment.
15) Possible requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
16) Primary immunodeficiency
17) Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
18) History of severe immediate hypersensitivity reaction to any of the agents used in this study
19) Live vaccine </= 6 weeks prior to planned start of conditioning regimen
20) 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.
21) 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-C19.
22) In the investigators 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.
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