Details

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 KITE 1415

CC 16-259

Hospital Main Campus

Stage Recurrent/Relapsed

Phase Phase 2

Disease Lymphoma, Mantle Cell

Drug KTE-C19

Description

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).
Secondary Objectives
  • 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

Inclusion Criteria

  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
  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 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
    • 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 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).
  7. Toxicities due to prior therapy must be stable and 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. 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 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 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
Exclusion Criteria

Exclusion Criteria

  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. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid 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, 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. Requirement for urgent therapy due to tumor mass effects e.g. bowel obstruction or blood vessel compression
  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.
  23. History of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years