Details
Title A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-C19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL) (ZUMA-2)
IRB KITE1415
CC 16-259
Hospital Main Campus
Stage Recurrent/Relapsed
Phase Phase 2
Disease Lymphoma - Mantle Cell
Drug KTE-C19
Description
Primary Objective- Evaluate the efficacy of KTE-C19, as measured by objective response rate, in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL).
- Assess the safety and tolerability of KTE-C19 and additional efficacy endpoints. The study will also assess the change in EQ-5D scores from baseline to Month 6.
Inclusion Criteria
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-, 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, defined by the following:
Disease progression after last regimen, or
Refractory disease is defined failure to achieve a partial response (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 1 lymph node should be ≥ 2 cm
105) For subjects in Cohort 1 and Cohort 2 only: Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (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 (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists).
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) Absolute neutrophil count (ANC) ≥ 1,000/μL
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.
Exclusion Criteria
201) History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease-free for at least 3 years
202) AutoSCT 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 re-treatment
205) Prior CAR 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 intravenous (IV) antimicrobials for management. Simple urinary tract infection (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 in-dwelling line or drain (eg, percutaneous nephrostomy tube, in-dwelling 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 (CSF) malignant cells or brain metastases or with a history of CNS lymphoma, CSF 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, 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 childbearing 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-up visits, or comply with the study requirements for participation.
223) History of autoimmune disease (eg Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
