Phase I Study Of The Administration Of Peripheral Activated T-Cells and EBV Specific CTLs Expressing CD19 Chimeric Receptors For Advanced B-Cell Non-Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia (ATECRAB)
N/A
N/A
Both
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Trial Information
Phase I Study Of The Administration Of Peripheral Activated T-Cells and EBV Specific CTLs Expressing CD19 Chimeric Receptors For Advanced B-Cell Non-Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia (ATECRAB)
The patient or their donor will give us blood to make CD19-CD28 chimeric receptor T cells
and CD19 chimeric-EBV specific T cells in the laboratory. These cells are grown and frozen
for the patient. Because the patient will have received cells with a new gene in them they
will be followed for a total of 15 years to see if there are any long term side effects of
gene transfer.
The patient will be assigned a dose of CD19-CD28 chimeric receptor-T cells and CD19 chimeric
receptor-EBV specific 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 patient's level of
circulating T cells is relatively high, they will receive one treatment of cyclophosphamide.
This drug will decrease the numbers of the patient's own T cells before we infuse the CD19
chimeric receptor T cells. Although we do not expect any effect on your tumor with the dose
that you will receive, this drug is part of many regimens that are used to treat lymphoma or
CLL. If you are already receiving chemotherapy, thi smay not be needed.
The patient will be given an injection of cells into the vein through an IV line at the
assigned dose. The patient will be followed in the clinic after the injection for up to 3
hours. 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),
they may be able to receive up to three additional doses of the T cells. These additional
infusions would be at least 4-6 weeks apart and at the same dose level the patietn received
the first time.
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
Medical tests during and after treatment:
The patient will receive standard medical tests when they are getting the infusions and
after: Physicalexams, 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 CD19-CD28 chimeric receptor T cells and CD19 chimeric
receptor-EBV specific T cells are working and how long they last in the body, extra blood
will be drawn at the following timepoints: On the day of the infusion blood will be taken
before the cells are given and several hours afterwards. Other blood will be drawn one week
after the infusion, 2 weeks, 4 weeks and 6 weeks after the infusion, every 3 months for 1
year, every 6 months for 4 years, then yearly for a total of 15 years.
Inclusion Criteria
INCLUSION CRITERIA:
FOR TREATMENT:
- Recurrent low or intermediate grade B-cell lymphoma or B-CLL, or newly diagnosed
patients unable to receive or complete standard therapy OR diagnosis of
relapsed/refractory intermediate B cell lymphoma with a treatment plan that will
include high dose therapy and autologous stem cell transplantation.
- CD19-positive tumor
- EBV seropositivity (in patient and donor, as applicable)
- Recovered from the acute toxic effects of all prior chemotherapy at least a week
before entering this study.
- Not be currently receiving any investigational agents or have not received any tumor
vaccines within the previous six weeks.
- No treatment with rituximab within the previous 8 weeks.
- ANC > 500, Hgb > 8.0*
- Bilirubin less than 3 times the upper limit of normal*
- AST less than 5 times the upper limit of normal*
- Serum creatinine less than 3 times upper limit of normal*
- Pulse oximetry of > 90% on room air*
- Adequate pulmonary function with FEV1, FVC and DLCO >35%* of expected corrected for
hemoglobin
- Karnofsky or Lansky score of > 60%.
- Available autologous or syngeneic transduced EBV-specific cytotoxic T lymphocytes and
peripheral blood T-cells with 15% or greater expression of CD19CAR determined by
flow-cytometry.
- Patients or legal guardians must understand and sign an informed consent indicating
that they are aware this is a research study and have been told of its possible
benefits and toxic side effects. Patients or their guardians will be given a copy of
the consent form.
- Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 3 months after the study is concluded. The
male partner should use a condom.
EXCLUSION CRITERIA:
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Active infection with HIV, HBV, HCV or CMV.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Evaluate safety of escalating doses of autologous or syngeneic peripheral blood T cells and EBV-specific cytotoxic CTLs, both genetically modified to express artificial T-cell receptors targeting the CD19 molecule.
Outcome Time Frame:
6 weeks
Safety Issue:
Yes
Principal Investigator
Carlos Ramos, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Baylor College of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
22899-ATECRAB
NCT ID:
NCT00709033
Start Date:
July 2000
Completion Date:
September 2028
Related Keywords:
- Non-Hodgkin Lymphoma
- Chronic Lymphocytic Leukemia
- refractory
- relapsed
- low
- intermediate-grade
- Non-Hodgkin lymphoma
- Chronic Lymphocytic Leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
Name | Location |
|---|---|
| Texas Children's Hospital | Houston, Texas |
| The Methodist Hospital | Houston, Texas 77030 |
