huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers

Inclusion criteria: 1. Signed informed consent form. 2. Male or female age ≥ 18 years. 3. HIV-1 infection diagnosed in accordance with WHO and CDC guidelines. This requires confirmation of the initial test result using a different qualified method from the initial assessment as follows: a. Any FDA approved rapid HIV test or HIV enzyme/chemiluminescence immunoassay (E/CIA) AND b. A second confirmatory test based on one of the following methods: i. Antibody test from a different manufacturer or based on different principles and epitopes (Note: Combination antigen-antibody-based rapid tests may be used); OR ii. HIV-1 antigen; OR iii. Plasma HIV-1 RNA viral load; OR iv. FDA approved Western blot. 4. Patients with one of the following B-cell malignancies: a. Non-Hodgkin's Lymphoma (NHL)- including the following sub-types: i. Patients with any of the following large B-cell lymphoma diagnoses who are relapsed/refractory after at least 2 prior lines of appropriate therapy: 1\. Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS); 2. Primary Cutaneous DLBCL; 3. Primary Mediastinal (thymic) Large B-cell Lymphoma; 4. ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); 5. High-grade B-cell Lymphoma, NOS; 6. T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; 7. Any aggressive B-cell lymphoma arising from indolent lymphoma. ii. Follicular Lymphoma (FL)- relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy). iii. Mantle Cell Lymphoma- relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Single agent monoclonal antibody therapy does not count towards prior lines of therapy. iv. Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Single agent monoclonal antibody therapy does not count towards prior lines of therapy. b. Chronic Lymphocytic Leukemia (CLL): i. Patients with relapsed/refractory disease after at least 2 prior lines of appropriate therapy; AND ii. Patients must have previously received or be intolerant to an approved BTK inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated. c. Richter's Transformation (RT; Large cell transformation of CLL)- Patients must be primary refractory or have received at least 1 prior line of treatment for Richter's Transformation. d. Acute Lymphoblastic Leukemia (ALL)- patients with 2nd or greater relapsed or refractory disease as defined by one of the following criteria: i. Recurrent disease in the blood or bone marrow identified morphologically, by IHC or flow; OR ii. 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 iii. 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 iv. Any relapse after allogeneic SCT; OR v. 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. vi. Note: Chronic myeloid leukemia (CML) lymphoid blast crisis is considered a sub-type of relapsed B-ALL, thus will be encompassed in our definition of B-ALL throughout 5. Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory. 1. NHL Patients: Within 6 months of physician-investigator confirmation of eligibility as long as there has been no intervening CD19 directed therapy since expression confirmed. Results outside of this window may be used, if there is no accessible tumor site and the subject did not receive intervening CD19 directed therapy since CD19 expression was confirmed. 2. CLL/RT/ALL Patients: At time of most recent relapse. If the subject has subsequently received CD19-directed therapy since this result was obtained, repeat testing must be performed to determine eligibility. 6\. Clinically stable on an antiretroviral therapy (ART) regimen, without changes within the 28 days prior to eligibility confirmation by a physician-investigator. No changes to the current ART regimen planned as confirmed by the participant's primary infectious disease physician. 7\. Viral Load ≤ 30 copies/mL by Hologic's Aptima® HIV-1 Quant Dx Assay within 30 days prior to physician-investigator confirmation of eligibility 8. ECOG Performance Status that is either 0 or 1. 9. Adequate organ function defined as: a. Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis b. ALT/AST ≤ 3x upper limit of normal c. Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl. d. Left Ventricle Ejection Fraction (LVEF) ≥40% confirmed by ECHO e. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air 10. Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility. 11\. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria: 1. Have no active GVHD and require no immunosuppression 2. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility Exclusion Criteria: 1. Active hepatitis B or active hepatitis C infection. 2. Any active, uncontrolled infection. 3. Class III/IV cardiovascular disability according to the New York Heart Association Classification. 4. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility. 5. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. 6. Active acute or chronic GVHD requiring systemic therapy. 7. Dependence on systemic steroids or immunosuppressant medications. 8. Receipt of prior huCART19-IL18 therapy. 9. 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. 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. 12. Current antiretroviral therapy (ART) regimen includes a non-nucleoside reverse transcriptase inhibitor (NNRTI). 13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40). 14. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.