Preliminary Safety and Tolerability of CD19x22 CAR T Cells in Adolescent and Adult R/R B-NHL Patients

Exclusion Criteria

• •1. Age \< 16 years of age.
• •2. Patient who is intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
• •3. History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.
• •4. Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.
• •5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen \[HBsAg\] positive) or hepatitis C.
• •6. History of known myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement.
• •7. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
• •8. Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment.
• •9. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• •10. Pregnancy (serum pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen); females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be childbearing potential.
• •11. Lactating.
• •12. 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.
• •13. Unwilling to participate in long-term follow-up protocol that is required if CAR T cell therapy is administered at CU Anschutz.
• •LYMPHODEPLETING CHEMOTHERAPY ELIGIILITY:
• •In order to proceed with lymphodepleting chemotherapy, enrolled participants must meet all eligibility criteria below within 72 hours prior to lymphodepletion, unless otherwise specified:
• •If the participant received bridging therapy after apheresis, confirmation of disease reevaluation is required. It must be within 6 weeks of initiation of LD chemotherapy.
• •* Confirmation that the participant has met the washout period for bridging therapy.
• •Negative serum pregnancy test (for women of childbearing potential)
• •Adequate organ function as defined by:
• •* Absolute neutrophil count (ANC) ≥ 500/μL.
• •* Platelet count ≥ 50,000/ μL.
• •* Renal: Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min.
• •* Hepatic: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).
• •* Total bilirubin ≤ 2 mg/dl, except in subjects with Gilbert's syndrome where a bilirubin \<3.0 will be acceptable.
• •* Pulmonary: No clinically significant pleural effusion and; Baseline oxygen saturation must be \> 92% on room air.
• •* Cardiac: Ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO) (only if subject received bridging anthracycline or developed a significant illness prior to LD-chemo per investigator assessment.) If clinically indicated, ECHO must be performed within 2 weeks prior to LD-chemotherapy.
• •CD19x22 CAR T CELL INFUSION ELIGIBILITY
• •In order to proceed with CD19x22 CAR T Cell Infusion, enrolled participants must meet all eligibility criteria below within 24 hours prior to CD19x22 CAR T Cell infusion, unless otherwise specified:
• •CD19x22 CAR T cells must have met manufacturing release criteria (unless prospectively approved by IND Sponsor, Gates Institute Medical Lead, and FDA).
• •Confirmation that the site has Anakinra and Ruxolitinib in stock and available (should IEC-HS treatment be required).
• •ECOG ≤2 or Karnofsky≥ 50%.
• •Clinically stable without evidence of vital sign instability, including the lack of supportive vasoactive drugs or intensive care unit support.
• •Oxygen saturation \> 92% on room air; cannot be on supplemental oxygen.
• •No evidence of uncontrolled, significant tumor lysis syndrome prior to cell infusion per investigator assessment.
• •No evidence of rapidly progressive NHL per investigator determination.
• •Participants' temperature is \<38.0 °C within 48 hours prior to cell infusion. (If the source of fever cannot be identified \[after thorough infectious disease work-up\], and the suspected cause is underlying malignancy, discussion and approval by the Gates Institute Medical Lead may allow continued infusion of CD19x22 cells. This should be appropriately documented in the patient's medical record.
• •Liver transaminase (ALT and AST) \< 5 x institutional ULN (\< grade 3) based on age- and laboratory- specific normal ranges.
• •Adequate renal function as defined by creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by the Cockcroft- Gault equation) ≥ 60 mL/min.
• •If these criteria are not met, measures can be taken to resolve the underlying condition(s). If successful, cells may be infused up to (and including) 7 days following the time of the planned infusion with no additional lymphodepletion. If the CD19x22 CAR T Cell infusion is delayed more than 7 days, lymphodepleting chemotherapy MAY be repeated, per the investigator's discretion. Prior to commencing a second round of lymphodepletion, participants must meet lymphodepletion criteria described above.