Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma (SAGAN)
Patients will give the investigators blood to make CD19 CD28 (with and without CD137)
chimeric receptor-T cells in the laboratory. These cells will be grown and frozen. To make
the T cells, investigators will take blood (or blood from a donor) and stimulate it with
growth factors to make the T cells grow. To get the CD19 antibody and CD28 (with or without
CD137) to attach to the surface of the T cell, they will insert the antibody gene into the T
cell. This is done with a virus called a retrovirus that has been made for this study and
will carry the antibody gene into the T cell. This virus also helps to find the T cells in
the blood after injecting them; in order to tell them apart investigators have made two
viruses that are slightly different because one has CD137. These two viruses can be told
apart by a special laboratory test. Because the patient will receive cells with a new gene
in them, the patient will be followed for a total of 15 years to see if there are any long
term side effects of gene transfer. If the patient cannot visit the clinic, he or she will
be contacted by the research coordinator or physician.
When subjects enroll on this study, they will be assigned a dose of CD19 chimeric receptor-T
cells. Several studies suggest that the infused T cells need room to be able to proliferate
and accomplish their functions and that this may not happen if there are too many other T
cells in circulation.
Because of that, if the subject's level of circulating T cells is relatively high, they may
receive one treatment of cyclophosphamide (Cytoxan) if the doctor thinks this is
appropriate. This drug will decrease the numbers of the subject's own T cells before
infusion of the CD19 chimeric receptor T cells. If subject is already receiving
chemotherapy, this may not be needed. The investigators would prefer subjects do not receive
other chemotherapy until 6 weeks after cell infusion but they can do so if their doctor
thinks it is medically necessary.
Patients will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take about 20 minutes. The investigators will follow them in the
clinic after the injection for up to 3 hours. If after a 4-6 week evaluation period after
the infusion, the subject seems to be experiencing a benefit, the subject may be able to
receive up to five additional doses of the T cells if they wish. These additional infusions
would be at least 4-6 weeks apart and at the same dose level received the first time or a
lower dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas
Children's Hospital or The Methodist Hospital.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of patients with dose limiting toxicity (DLT)
Toxicity will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 4. DLT will be defined as any of the following that is NOT (1) pre-existing, or (2) due to infection (to which patients with CLL and NHL are predisposed), or (3) due to underlying malignancy, and that may, after consultation with the FDA when indicated, be considered possibly, probably, or definitely related to the study cellular products: (1) Non-hematologic DLT is any grade 3 or grade 4 non-hematologic toxicity, including allergic reactions to T cell infusions; (2) Hematologic DLT is defined as any grade 4 hematologic toxicity. Patients with evidence of bone marrow disease (metastases or diffuse infiltration) are not evaluable for hematologic dose limiting toxicity.
Carlos A Ramos, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|