Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies

Inclusion criteria.

• Disease Status
• Disease Status of ALL
• Must have chemotherapy refractory disease defined as progression or stable disease after two lines of therapies, or relapsed disease after achieving CR.
• Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD on two occasions at least 2 weeks apart.
• Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
• Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR) are eligible.
• Disease Status of aggressive B-cell NHL •Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008: oDLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR oprimary mediastinal (thymic) large B cell lymphoma; OR otransformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL; OR oFollicular Lymphoma Grade 3B •Subjects with DLBCL, Follicular Lymphoma Grade 3B -or-

Subjects with transformed FL, MZL, or CLL/SLL who HAVE NOT received chemotherapy prior to transformation:

oMust have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of DLBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant.

•Subjects with transformed FL, MZL, or CLL/SLL who HAVE received anthracycline-containing chemotherapy prior to transformation: oMust have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.

• Measureable Disease
• Subjects with ALL: must have evaluable or measurable disease (MRD positive by flow cytometry, NGS, or PCR is acceptable).
• Subjects with aggressive B-cell NHL: must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma[38]. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• CD22 expression

•Subjects with ALL: CD22 positive expression on malignant cells is required and must be detected by immunohistochemistry or flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject.

CD22 expression must be demonstrated subsequent to any anti-CD22 targeted therapy (e.g. Moxetumomab pasudotox or inotuzumab ogozamicin) in subjects with ALL.

•Subjects with aggressive B-cell NHL: CD22 expression at any level, including undetectable, will be acceptable. Subjects must have archival tissue available for analysis of CD22 expression or must be willing to undergo a biopsy of easily accessible disease.

• Prior Bone Marrow-Stem Cell Transplant Subjects who have undergone autologous SCT with disease progression or relapse following SCT are eligible. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have no evidence of GVHD and have been without immunosuppressive agents for at least 30 days.
• Prior Therapy Wash-out At least 2 weeks or 5 half lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half lives.

Exceptions:

• There is no time restriction with regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such;
• Subjects receiving h