Details

Details

Title 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)

IRB KITE1414

CC 15-703

Hospital Main Campus

Phase Phase 1, Phase 2

Disease Blood & Marrow Transplant (BMT), Lymphoma - Non - Hodgkin

Drug KTE-C19

Description

Description

Objectives
  • The primary objective of phase 1 is to evaluate the safety of KTE-C19 regimens.aa
  • The primary objective of phase 2 is to evaluate the efficacy of KTE-C19, as measured by objective response rate in subjects with DLBCL, PMBCL, and TFL. Secondary objectives will include assessing the safety and tolerability of KTE-C19 and additional efficacy endpoints.
Inclusion Criteria

Inclusion Criteria

  1. Histologically confirmed aggressive B cell NHL, including the following types defined by WHO 2008:
    • 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
  2. 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
      • SI 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 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
  3. Subjects must have received adequate prior therapy including at a minimum:
    • Anti-CD20 monoclonal antibody unless investigator determines that tumor 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
  4. At least 1 measureable 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
  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
  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 or older
  9. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  10. ANC ≥ 1000/uL
  11. Platelet count ≥ 100/uL
  12. 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, and no clinically significant ECG findings
    • No clinically significant pleural effusion
    • Baseline oxygen saturation > 92% on room air
  13. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical steralization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
  14. Relapsed transplant ineligible DLBCL, PMBCL, or TFL (must have biopsy proven recurrence in relapsed subjects)
Exclusion Criteria

Exclusion Criteria

  1. 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
  2. History of Richter's transformation of CLL
  3. Autologous stem cell transplant within 6 weeks of planned KTE-C19 infusion
  4. History of allogeneic stem cell transplantation
  5. Prior CD19 targeted therapy with the exception of subjects who received KTE-C19 in this study and are eligible for re-treatment
  6. Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
  7. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
  8. 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.
  9. Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  10. 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
  11. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases
  12. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
  14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  15. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression
  16. Primary immunodeficiency
  17. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
  18. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
  19. History of severe immediate hypersensitivity reaction to any of the agents used in this study
  20. Live vaccine ≤ 6 weeks prior to start of conditioning regimen
  21. 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
  22. 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
  23. 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