CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

Inclusion Criteria:

Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:

Philadelphia chromosome negative acute lymphoblastic leukemia:

Beyond first complete remission (CR) at the time of pre-transplant evaluation
Required > 1 cycle of induction chemotherapy to achieve CR
First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis
Planned for or have had a reduced intensity conditioned or non-myeloablative transplant

Philadelphia positive acute lymphoblastic leukemia

Not in CR at the time of pre-transplant evaluation

In CR with the following features:

Intolerant or unwilling to use a TKI after HCT
Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods

Chronic lymphocytic leukemia, or low grade B cell lymphomas:

Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node >= 5 cm at the time of pre-transplant evaluation

Mantle cell lymphoma:

Failed or ineligible for autologous transplant AND a lymph node >= 2 cm at the time of pre-transplant evaluation

Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas

Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation
Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
The patient has signed the informed consent form for this study
DONOR: Genotypic or phenotypic HLA-identical family members

DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:

CMV seropositive and HLA-A*0101 positive
CMV seropositive and HLA-A*0201 positive
CMV seropositive and HLA-B*0702 positive
CMV seropositive and HLA-B*0801 positive
EBV seropositive and HLA-A*0201 positive
EBV seropositive and HLA-B*0801 positive
DONOR: Hematocrit >= 35% at enrollment
DONOR: Age >= 18 years
DONOR: The donor has signed the informed consent form for the study

Exclusion Criteria:

Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
Human immunodeficiency virus (HIV) seropositive
Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
Pregnant or breast-feeding
DONOR: G-CSF administered within one month prior to the blood draw for T cell collection
DONOR: Unable for any reason to provide a 400 ml blood draw
DONOR: Inadequate peripheral veins for blood collection
DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive
DONOR: Active hepatitis B or hepatitis C virus infection
DONOR: Positive serologic test for syphilis
DONOR: Aberrant CD45RA isoform expression on all T cells
DONOR: Systolic blood pressure (BP) < 80 or > 200
DONOR: Heart rate < 50 or > 120, if considered due to cardiac disease
DONOR: Oxygen (O2) saturation < 88% on room air
DONOR: Serum creatinine (Cr) > 3.0
DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x the upper limit of normal
DONOR: Unable to provide informed consent to participate
DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors
DONOR: Pregnant or nursing