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Treatment of High Risk Acute Leukemia With CD40 Ligand and IL-2 Gene Modified Autologous Skin Fibroblasts and Tumor Cells

Phase 1
75 Years
Not Enrolling

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Trial Information

Treatment of High Risk Acute Leukemia With CD40 Ligand and IL-2 Gene Modified Autologous Skin Fibroblasts and Tumor Cells

Before starting in the treatment part of this study, leukemia cells and skin fibroblasts
will be collected from the patient - called "procurement" - to allow us to make the vaccine.
These leukemia cells are taken from either peripheral blood, leukopheresis product or bone
marrow. The fibroblasts will be prepared in the laboratory with specially produced human
viruses (adenoviruses) that carry the IL-2 or the CD40L gene. The viruses will "drop off"
the genes inside the fibroblasts. The CD40L and IL-2 genes are meant to help stimulate the
immune system to fight the leukemia. The modified fibroblasts will be injected with a number
of leukemic cells under the skin. All the cells will be irradiated before injection to stop
them growing. Patients will receive three shots. Depending on the response, patients may be
able to have three additional shots.

In order to collect the skin fibroblasts at the very beginning of the study, and then during
the study, we will perform small skin biopsies. In particular before the second shot, and
then again about 1 week later, we will look for both the modified and leukemia cells that
have been re-injected under the skin. We will do this by taking a skin biopsy from the place
where the cells were injected. The area where the skin biopsy will be obtained will be
sterilized and then numbed with a local acting agent. The skin will be removed with a
"tissue punch" which will cut a circle of approximately 1/4th of an inch into the skin. The
site where the skin was removed will be closed with suture, tape or stitches. The area will
be covered with dry gauze and adhesive tape. These tests are to see whether the shots are
killing leukemia cells and to make sure leukemia cells are not growing at the injection

To study how the immunity is working in the system, we will take blood samples before 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 samples will be approximately 1 tablespoons
of blood, 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.

Also, patients will need to have a bone marrow test before enrolling on the study and at
week 12. If the patient is not responding, they may have treatment with other chemotherapy
or radiation. Patients will need to come to the clinic on the days of blood drawing and to
be seen at Texas Children's Cancer Center/The Methodist Hospital at weekly intervals for 10
weeks, then every other week for 6 weeks, and then monthly for a year. Thereafter, patients
will either be seen in the clinic or contacted by one of the research staff working on this
study once a year for 15 years. Additional visits may be necessary.

Inclusion Criteria:

1. Patients less than or equal to 75 years old with lymphoid (pre-B, B, T, non B-, non
T, or Burkitt if bone marrow blasts > 20%) or acute myeloid leukemia (M0 to M7) or
myelodysplastic syndrome and with: Disease that has entered remission with
chemotherapy and/or bone marrow transplantation, but is considered to be at high risk
of relapse. or Primary, or relapsed treatment-refractory disease who, at the time of
reinjection of the tumor vaccine, are at a state of complete or partial cytological
remission disease (<20% blasts infiltrating the bone marrow) after a second/higher
line of conventional and/or high dose chemotherapy.

2. Patients must have a life expectancy of at least 10 weeks.

3. Patients must have ECOG performance status of 0-2 as below:

4. Patients must have recovered from the toxic effects of all prior chemotherapy before
entering this study, and have an absolute neutrophil count >500/mm3, absolute
lymphocyte count >200/mm3, and platelet count >50,000/mm3.

5. Patients must not have active GvHD at the time of protocol entry.

6. Patient has not received high dose steroids within the last week or other
immunosuppressive drugs within a week (or longer as indicated by the half life of the

7. Patients must not be infected at time of protocol entry, and should not be receiving
antibiotics (other than prophylactic Septra.)

8. Patients must not be HIV-positive.

9. Patients must have adequate liver function (bilirubin<1.5 mg% SGOT<2x normal, normal
prothrombin time).

10. Patients must have transduced cells available that are demonstrably >20% CD40L
expressing fibroblasts and producing>150 pg IL-2/10 6 cell/24 hr.

11. Patients or legal guardians 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 or their guardians will be given a copy of the consent form.

12. Patient must not have received treatment with other investigational agents within the
last 4 weeks.

13. 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:

1. Rapidly progressive/refractory disease (>20% blasts infiltrating the bone marrow)

2. Life expectancy < 10 weeks

3. Active infection

4. Need for concomitant drugs except analgesics

5. Pregnancy or lactation

6. Seropositive for HIV

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

• To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL

Outcome Time Frame:

15 years

Safety Issue:


Principal Investigator

Malcolm K Brenner, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Texas Children's Hospital


United States: Food and Drug Administration

Study ID:

H6408-Leu Leu



Start Date:

June 1999

Completion Date:

June 2010

Related Keywords:

  • Leukemia
  • Leukemia



Texas Children's Hospital Houston, Texas  
The Methodist Hospital Houston, Texas  77030
Texas Children's Hospital GCRC Houston, Texas  77030