Treatment of Chronic Lymphocytic B-Leukemia (B-CLL) With Human IL-2 Gene Modified and Human CD40 Ligand-Expressing Autologous Tumor Cells
18 Years
N/A
Both
Chronic Lymphocytic B-Leukemia
Trial Information
Treatment of Chronic Lymphocytic B-Leukemia (B-CLL) With Human IL-2 Gene Modified and Human CD40 Ligand-Expressing Autologous Tumor Cells
Before starting treatment some of the cancer cells will be taken from the patient and
separated in the laboratory. A specially produced human virus (adenovirus) that carries the
IL-2 gene will be put into the cells. The rest of the cancer cells will be stimulated to
express on their surface a substance called the human CD40 ligand. These substances (IL-2
and CD40L), already naturally present in the body, are meant to help the immune system fight
the cancer.
In this study, the modified cancer cells will be injected under the skin. There will be up
to six shots. We do not know the best amount of special cells to use, so different patients
will get different numbers of cells.
After the first three shots (if more modified cancer cells are available), patients may be
able to have three additional shots. After they have received six shots, they may be able to
have additional shots if the cancer has gotten smaller and more of the cells are available.
A complete history and physical examination is necessary before a patient can be enrolled in
the study. A physical examination will also be performed weekly for ten weeks after the
injection, then on week twelve, then monthly for one year. Patients will then have yearly
checkups for the next fifteen years. After the first and second shots, we will remove some
of the modified cells that have been injected under the skin, to study them. We will do this
by removing a section of skin (referred to as a skin biopsy) at the place where the cells
were injected. These tests will help us to see whether or not the modified cells are killing
cancer cells and whether or not the cancer cells are growing. If we suspect the cancer cells
are growing, we may repeat this procedure after the third and fourth shots.
To study how the immunity is working in the patients system, we will take blood samples
before the first injection, then weekly for 10 weeks, on week 12, once a month for a year,
and then eventually once a year for fifteen years. These blood samples must be taken at The
Methodist Hospital. The total amount of blood that will be obtained is approximately two to
three tablespoonfuls, which is considered a safe amount. If the patient has additional
injections, blood will be drawn prior to each injection. Additional office visits may be
necessary.
If the patient decides to withdraw at any time during the study both samples and data
collected during the study will be maintained with identifiers for safety reasons.
Inclusion Criteria:
- Patients are eligible for administration of their vaccine if they present with B-CLL
(not in Richter's transformation) with (group A) or without (group B) measurable
disease. Untreated or complete remission patients will be enrolled for vaccine
administration in a therapeutic (i.e. no chemotherapy) window of three months. If
during these three months (necessary to complete the vaccine study) the patient
presents with rapid clinical progression, he or she will be excluded from our current
study and will receive treatment according to the standard institutional guidelines.
IMPORTANT NOTE: Vaccine production for complete remission patients can only be
achieved if tumor cells have been collected BEFORE entering complete remission.
- Patients must have a life expectancy of at least 10 weeks.
- Patients must have ECOG performance status of 0-2.
- Patients must have recovered from the toxic effects of all prior chemotherapy before
entering this study, and must have an absolute neutrophil count of >/= 500/uL,
absolute lymphocyte count >/= 200/uL, hemoglobin >/= 8g/dL and platelet count >/=
50,000/uL.
- Patients must not be infected at time of protocol entry, and should not be receiving
antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
- Patients must be HIV-negative.
- Patients must be willing to practice appropriate birth control methods during the
study and for 3 months after the study is concluded.
- Patients must not be suffering from an autoimmune disease (including active
graft-versus-host disease-GvHD, refractory immune thrombocytopenia-ITP or refractory
autoimmune hemolytic anemia-AIHA) and should not be receiving immunosuppressive
drugs.
- Patients must have adequate liver function (total bilirubin times normal, normal prothrombin time).
- Patients must have adequate renal function (creatinine < 3 times normal for age or
creatinine clearance > 80mg/min/1.73m2).
- Patients must 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 will be given a copy of the consent form.
- Patient must not have received treatment with other investigational agents within the
last 4 weeks.
Exclusion Criteria:
- Richter's transformation (aggressive non-Hodgkin's lymphoma)
- active infection
- significant autoimmune disease (including active GvHD, ITP and AIHA)
- requirement for immunosuppressive drugs
- inadequate liver and/or renal function
- pregnancy or lactation
- refusal to practice birth control methods
- seropositive for HIV
- life expectancy less than 10 weeks
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety of 3-6 SQ injections of autologous malignant B cells from chronic B-CLL pts, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
Outcome Time Frame:
3 mths
Safety Issue:
Yes
Principal Investigator
Malcolm K Brenner, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Center for Cell and Gene Therapy, Baylor College of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
H11541
NCT ID:
NCT00058786
Start Date:
December 2002
Completion Date:
March 2010
Related Keywords:
- Chronic Lymphocytic B-Leukemia
- Leukemia
Name | Location |
|---|---|
| The Methodist Hospital | Houston, Texas 77030 |
