Study of Gelonin Purging of Autologous Stem Cells for Transplantation

Treatment:

The HuM195-Gelonin conjugate has been designed to target leukemia cells and destroy them.

This treatment is divided into 3 parts.

Part I:

MOBILIZATION and STEM CELL COLLECTION:

This is the process that allows for collection of the autologous stem cells (the cells that
will be used to do the transplant). All participants will receive the drug idarubicin by vein
for 3 days together with cytarabine by vein for 3 days. This will be followed by injections
of filgrastim (Neupogen) under the skin twice a day until the white count has recovered and
the stem cells are collected. During the process, the number of stem cells in the blood will
be measured. When the number of cells reach a certain level, participants will go through a
collection procedure known as apheresis.

The apheresis procedure includes collecting blood through a large catheter placed under the
collarbone or in the arm with the assistance of a device known as a cell separator. This
device separates the stem cells from the rest of the blood and returns the rest of the blood
to the participant. The procedure is usually done as an outpatient and takes between 4-5
hours to perform. Most patients collect enough cells for a transplant after 1 or 2
procedures. In this study, a maximum of 5 procedures are allowed.

Participants who are unable to have enough cells collected to take part in the study
procedures, will be taken off study and offered alternative standard or investigational
therapy. Participants will be able to leave the hospital with physician approval. They will
then be monitored on a daily basis until the white blood cell count has recovered (usually
4-5 weeks). The stem cell collection can be done as either an inpatient or outpatient
procedure depending on the participant's condition.

Part II:

PURGING PROCEDURE:

The stem cells that are collected through the apheresis procedure are treated in the
laboratory with the Hum195/Gelonin conjugate. This procedure is known as purging and it is
being studied to learn if the treatment of the stem cells with the HuM195/Gelonin conjugate
can eliminate leukemia cells without damaging the normal stem cells. Since the best dose of
HuM195/Gelonin conjugate for purging is not known, the cells of the participants in this
study will receive 1 of 3 different doses of HuM195/Gelonin. The dose of HuM195/Gelonin that
the cells will receive will be decided randomly according to the experience of the
participants treated earlier in the study.

The first 3 participants in this study will receive cells that have not been treated with
HuM195/Gelonin

After the cells have been treated, they are frozen for future use after the high dose
busulfan treatment is given. As a safety measure, all participants will need to have a
proportion of untreated stem cells as a back up. These can come from the original stem cell
harvest or from a bone marrow harvest.

Part III:

HIGH DOSE FLUDARABINE/BUSULFAN WITH AUTOLOGOUS STEM CELL TRANSPLANT:

All participants who had enough cells treated with HuM195-Gelonin conjugate will then receive
busulfan. Busulfan will be given by vein once a day for four days. It will be given together
with fludarabine by vein once a day for 4 days. Three days after participants receive the
last dose of busulfan, they will receive their previously stored stem cells through a blood
transfusion. All participants will receive supportive care. This will include antibiotics,
transfusions of blood products, extra nutrients, pain medication, and medications that will
quicken the recovery of white blood cells. Participants will be on study for at least 12
months after the stem cell transplant coming for regular check ups.

All participants will have busulfan blood levels checked at specific times before, during and
after busulfan infusion. On occasion more blood levels may be drawn. Levels are drawn through
a small needle placed in the hands or arms of the patients and removed after the last
busulfan blood draw. The busulfan dose administered MAY be modified according to the levels
to prevent side effects. Two teaspoons of blood will be drawn for these measurements each
time.

Participants will remain in the hospital for about 4-6 weeks and as an outpatient for 1 to 3
months. After participants leave the Medical Center Area, they will be seen in the transplant
center every 3 to 6 months for 2 years.

This is an investigational study. The FDA has authorized the use of the HuM195-Gelonin
conjugate in research only. Fludarabine has been previously approved for treatment of chronic
lymphocytic leukemia by the FDA. The injectable solution of busulfan is a new preparation
that has been approved by the FDA for allogeneic transplantation for chronic myelogenous
leukemia (CML). The use of these drugs in this study is investigational. Up to 24 patients
will be enrolled on this study. All will be enrolled at UTMDACC.

Inclusion Criteria:

- Patients with AML, RAEB-t, RAEB, or CMML who are in first remission and have poor
prognosis cytogenetic abnormalities (i.e: deletions of chromosome 5, 7, 20; trisomy 8,
t9,22,11q23 abnormalities or complex karyotypes).*

- Patients with AML, RAEB-t, RAEB, or CMML who are in second or subsequent remission.

- Remission is defined as ANC>1.5 x 109/Lt; Platelet count >100 x 109/Lt, and red cell
transfusion independence.

- Male or female who have provided written informed consent.

- Tumor cells must be > 80 % CD-33 positive by flow cytometry.

- For women of childbearing potential (i.e., exclude post-menopausal women, women who
have been surgically sterilized), adequate birth control methods must be used.
Acceptable birth control methods are limited to oral contraceptives, implants,
diaphragm, IUD or spermicide used with a condom)

- No chemotherapy for the two weeks prior to entering the study.

- No evidence of residual toxic effects from prior chemotherapy.

- Patients with proven bacterial infection are not eligible until resolution of the
infection (patient afebrile, not on steroids). Patients with active fungal infections
are eligible only if evidence of response to antifungal medications is documented and
they do not have fever exceeding 38C.

- Must have at least 5 x 106 CD34+ peripheral blood stem cells collected.

- All patients who have had less than 7 x 106 CD34+ cells/kg collected, should have a
bone marrow harvest to serve as back-up.

- A minimum of 1 x 106 CD34+ cells/kg of unpurged bone marrow or 2 x 106 CD34+ cells/kg
of unpurged peripheral blood need to be stored as backup to be eligible for this
protocol.

- Patients must have bilirubin less than 2.0, transaminases less than 4 x upper limit of
normal.

- Pulmonary function tests >50% predicted for DLCO, FVC and FEV1

- No active uncontrolled infection

- No active CNS disease

- No uncontrolled arrythmias

- Zubrod Performance Status less than or equal to 2

Exclusion Criteria:

- Active CNS disease