Clinical Trial Detail

This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.

Ages Eligible for Study: 18 Years to 75 Years

Genders Eligible for Study: Both

- 1. Patients with

- a) CD19+ B cell malignancy who have persistent, relapsed or progressive disease after peripheral blood stem cell transplant from an HLA-matched related donor

-OR

- b) CD19+ B cell malignancy who are planned for or have had a peripheral blood stem cell transplant from an HLA-matched related donor after myeloablative or non-myeloablative conditioning on a FHCRC transplant protocol and are at high risk of relapse after HCT defined by any one of the disease-specific criteria listed below:

-- a. Philadelphia chromosome negative acute lymphoblastic leukemia:

--- i. Beyond first complete remission (CR) at the time of pre-transplant evaluation

--- ii. 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) prior to transplant

--- iii. First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis

-- b. Chronic lymphocytic leukemia, or low grade B cell lymphoma: Lymph nodes greater than or equal to 5 cm at the time of pre-transplant evaluation

-- c. Mantle cell lymphoma: Lymph nodes greater than or equal to 2 cm at the time of pre-transplant evaluation

-- d. Diffuse large B cell lymphoma, large B cell transformation of an indolent lymphoma or other large B cell lymphoma: Not in CR by conventional computed tomography (CT) criteria or in CR by conventional criteria but with evidence of residual disease by a positive positron emission tomography (PET) scan

- 2. 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

- 3. 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

Other eligibility criteria may apply.

- Philadelphia chromosome positive acute lymphocytic leukemia

- 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

Other exclusion criteria may apply.