Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant

Background: CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL). Objective: To test whether it is safe to give anti-CD22 CAR T cells to people with HCL. Eligibility: Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer. Design: Participants will be screened with the following: Medical history Physical exam Blood and urine tests Biopsy sample Electrocardiogram Echocardiogram Lung function tests Imaging scans Some screening tests will be repeated during the study. Participants may need to have a catheter placed in a large vein. Participants will have magnetic resonance imaging of the brain. Participants will have a neurologic evaluation and fill out questionnaires. Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant. Participants will get infusions of chemotherapy drugs. Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month. After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.

* INCLUSION CRITERIA * Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of WHO classification \[WHO, 2008 revised 2016\] of lymphoid neoplasm. * Participants should have any of the following indications for therapy: * ANC \5/nL in blood or \>25/mm\^3 in CSF, * HCL/HCLv count doubling time \=18 years * ECOG performance \=60%, see Appendix A), participants are exempt from this criterion if poor performance status is related to HCL. * Participants must have adequate organ function as defined below: Participants must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. If participants exhibit minor lab abnormalities that are determined to be related to HCL (not therapy-related), then those participants will be allowed to participate * Total bilirubin \ 5) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \ 2 g/dL * Prothrombin time (PT)/International Normalized Ratio (INR) \< 2.5x ULN (if on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, PT \< 2.5x ULN * Fibrinogen \>= 0.5x lower limit of normal * Participants with CNS disease are eligible, with exceptions * Participants with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active graft-versus-host disease (GVHD) and no longer taking immunosuppressive agents for at least 30 days prior to initiation of study intervention. * Women of childbearing potential (WOCBP) must agree to use effective contraception (barrier, hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy or 4 months after cells infusion, whichever is later. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drug. * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of study drug. * Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA * Pregnancy * Systemic chemotherapy, immunotherapy, or radiation therapy \= 5% by flow cytometry) * Seropositive for human immunodeficiency virus (HIV) antibody. (Participants with HIV are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy in the future should study results indicate effectiveness.) * Seropositive for hepatitis C virus (HCV) or positive for hepatitis B surface antigen (HbsAG). Participants who convert to negative will not be excluded for history of positive test. * Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, asthma, chronic obstructive pulmonary disease, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject * History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells (i.e., gentamicin)