Phase I Study of Adoptive Transfer of Autologous T Lymphocytes Engrafted With a Chimeric Antigen Receptor Targeting the Kappa Light Chain of Immunoglobulin Expressed in Patients With Chronic Lymphocytic Leukemia, B-Cell Lymphoma or Multiple Myeloma
To get the kappa antibody (with CD28) to attach to the surface of the T cell, we inserted
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 us find the T cells in the patient's blood after we inject them. Because the patient
has received cells with a new gene in them patients will be followed for a total of 15 years
to see if there are any long term side effects of gene transfer.
When you enroll on this study, patients will be assigned to one of three groups of different
doses receiving kappa-CD28 T cells.
Several studies suggest that the infused T cells need room to be able to grow 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 level of circulating T cells is relatively high or the
patient has B-CLL, the patient may receive one treatment of cyclophosphamide four to seven
days prior to the infusion of the T cells. This drug will decrease the numbers of the
patients own T cells before we infuse the kappa-CD28 T cells. Although we do not expect any
effect on the tumor with the dose that the patient will receive, this drug is part of many
regimens that are used to treat lymphoma, MM or CLL.
Patients will be given an injection of cells into the vein through an IV line at the
assigned dose. If you were given cyclophosphamide as stated above, the T-cells will be given
4-7 days after the cyclophosphamide. If the patient has recently received other
chemotherapy, the T-cells will be given at least 4 days after the last chemotherapy. We
would prefer that patients not receive other chemotherapy until 6 weeks after the cell
infusion but they can do so if their doctor thinks it is medically necessary. If the patient
recently had a stem cell transplant, the T-cells will be given 14-60 days after the
transplant. Before the patient receives the injection, they will be given a dose of Benadryl
and Tylenol. The injection will take about 20 minutes. We will follow the patient in the
clinic after the injection for up to 3 hours. The treatment will be given by the Center for
Cell and Gene Therapy at Texas Childrens Hospital or The Methodist Hospital.
If after a 4-6 week evaluation period after the infusion, the patient seems to be
experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms),
the patient may be able to receive up to three 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 they
received the first time or a lower dose.
Medical tests before treatment—
- Before being treated, the patient will receive a series of standard medical tests:
- Physical exam
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by scans and/or bone marrow studies (to include a chest x ray
at pre-infusion if not already done)
Medical tests during and after treatment—
Patients will receive standard medical tests when they are getting the infusions and after:
- Physical exams
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by scans and/or bone marrow studies 6 weeks after the
infusion
To learn more about the way the kappa-CD28 chimeric receptor T cells working and how long
they last in the body, extra blood will be drawn. The total amount on any day is about 10
teaspoons. This volume is considered safe, but may be decreased if the patient is anemic.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluate safety of auto T cells genetically modified to express chimeric antigen receptors targeting the kappa-light chain of human immunoglobulin in pts with CLL, B cell non-Hodgkin Lymphoma or Multiple Myeloma whose tumors express Kappa-light chain.
6 weeks
Yes
Carlos Ramos, MD
Principal Investigator
Baylor College of Medicine/Texas Children's Hospital
United States: Food and Drug Administration
H-23574-CHARKALL
NCT00881920
July 2009
July 2030
Name | Location |
---|---|
Texas Children's Hospital | Houston, Texas |
The Methodist Hospital | Houston, Texas 77030 |