huCART19-IL18 in CD19+ Cancers

Eligibility Criteria

• 1. Signed informed consent form
• 2. Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory
• 3. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
• 4. Adequate organ function defined as:
• 5. Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility. .
• 6. Male or female age ≥ 18 years.
• 7. ECOG Performance Status that is either 0 or 1.
• 8. Subjects of reproductive potential must agree to use acceptable birth control methods.
• 9. Disease-specific criteria:
• 1. Patients must have either relapsed after, or be ineligible for, prior CAR T cell therapy, and meet one of the following criteria:
• 1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy; OR
• 2. Relapsed/refractory disease after autologous SCT; OR
• 3. Relapsed/refractory disease after allogeneic SCT. ii. Follicular lymphoma
• 1. Patients must have either relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
• 2. Received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy) and progressed within 2 years after second or higher line of therapy.
• 1. Patients must have either failed standard of care CAR T cell therapy (e.g., Tecartus™, etc) or other investigational CAR T cell product, OR be ineligible for standard of care Tecartus™; and
• 2. Patients must also meet one of the following criteria:
• 1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy; OR
• 2. Relapsed/refractory disease after prior autologous SCT; OR
• 3. Relapsed/refractory disease after prior allogeneic SCT.
• 1. Patients with relapsed/refractory disease after at least 2 prior lines of appropriate therapy; AND
• 2. Patients must have previously received or be intolerant to an approved BTK inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated.
• 1. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.
• 1. Recurrent disease in the blood or bone marrow identified morphologically, by IHC or flow; OR
• 2. Isolated CNS disease. Note: Patients with prior/current history of CNS3 disease will only be eligible for treatment if the CNS disease is responsive to therapy; OR
• 3. Recurrent extramedullary disease at other (non-CNS) sites if disease response can be assessed radiographically. Note: Patients with recurrent extramedullary disease do not need to have detectable blood or bone marrow involvement; OR
• 4. Any relapse after allogeneic SCT; OR
• 5. Patients with refractory disease as defined by one of the following:
• 1. Failure to achieve remission (\<5% bone marrow blasts or ongoing extramedullary or CNS disease) after 2 cycles of induction chemotherapy; OR
• 2. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.
• 1. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
• 2. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• 3. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• 4. Active acute or chronic GVHD requiring systemic therapy.
• 5. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
• 6. RETIRED WITH PROTOCOL AMENDMENT V7
• 7. Receipt of prior huCART19 therapy.
• 8. CNS disease as defined by disease-cohort as follows:
• 1. NHL/CLL Patients: Active CNS disease. Note: Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• 2. ALL Patients: CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• 9. Pregnant or nursing (lactating) women.
• 10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
• 11. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.