Feasibility and Safety of Collecting and Combining Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy in Subjects with Relapsed/Refractory Hematological Malignancies

Inclusion Criteria:

• Age 18 - 85 years.

• Histologically proven hematological malignancy according to the World HealthOrganization 2016 classification criteria for which a commercially available,FDA-approved CAR T product exists.

• Relapsed or refractory disease, defined by the following:

• Disease progression after last regimen, or

• Refractory disease: failure to achieve a partial response (PR) or completeremission (CR) to the last regimen

• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since anyprior systemic therapy for the malignancy at the time the subject is planned forleukapheresis.

• Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 with theexception of alopecia.

• Subjects with an active uncontrolled infection should not start CAR T treatmentuntil the infection has resolved.

• Eastern cooperative oncology group (ECOG) performance status 0 - 2.

• Adequate hematologic, hepatic, and cardiac function

• Serum pregnancy test for women of childbearing potential (WOCBP) at Screening.

• Willing to comply to research specimen collection as specified in the protocol.

• Written informed consent obtained from subject and ability for subject to complywith the requirements of the study.

Exclusion Criteria:

• Autologous hematopoietic cell transplant intent or execution within 8 weeks ofplanned CAR T infusion.

• History of allogeneic cell transplantation within 8 weeks of planned CAR T infusion.

• Presence or suspicion of fungal, bacterial, viral, or other infection that isuncontrolled or requiring IV antimicrobials for management at time of screening.

• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina,or other clinically significant cardiac disease within 6 months of enrollment.

• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, or anyautoimmune disease with CNS involvement.

• Doses of corticosteroids of greater than or equal to 5 mg/day of prednisone orequivalent doses of other corticosteroids and other immunosuppressive drugs are notallowed prior to enrollment. A washout period of 10 days prior to leukapheresis and 10 days prior to anti-CD19 CAR T cell administration is required.

• Any medical condition likely to interfere with assessment of feasibility or safetyof study treatment.

• Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen.

• History of severe immediate hypersensitivity reaction to any of the agents used inthis study.

• Current pregnancy or breastfeeding because of the potentially dangerous effects ofthe preparative chemotherapy on the fetus or infant.

• Subjects of both sexes who are not willing to practice birth control from the timeof consent through 6 months after the completion of conditioning chemotherapy.Females who have undergone surgical sterilization or who have been postmenopausalfor at least 1 year are not considered to be of childbearing potential.

• In the investigator's judgment, the subject is unlikely to complete allprotocol-required study visits or procedures, including follow-up visits, or complywith the study requirements for participation.

• Patients with obvious myeloid clonal hematopoiesis on the screening bone marrowbiopsy will be excluded based on the risk of developing myeloid neoplasms with aHSCinfusion.