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Dose Finding Study of Gelonin Purging of Autologous Stem Cells for Transplantation of Patients With AML/MDS in First or Subsequent Remission

Phase 1/Phase 2
Not Enrolling
Acute Myelogenous Leukemia, Myelodysplastic Syndrome

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Trial Information

Dose Finding Study of Gelonin Purging of Autologous Stem Cells for Transplantation of Patients With AML/MDS in First or Subsequent Remission


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

This treatment is divided into 3 parts.

Part I:


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:


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

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:


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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Optimal Dose Gelonin

Outcome Description:

Dose-finding success, defined as patient alive and engrafted at day 28 post transplant, represented as number of patient successes with 3 differing doses (5, 10, or 15 nanomolar (nm) gelonin-antiCD33 purged autologous stem cells after a high dose fludarabine/busulfan conditioning regimen).

Outcome Time Frame:

28 days post transplant

Safety Issue:


Principal Investigator

Sergio A. Giralt, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2002

Completion Date:

March 2005

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • AML
  • MDS
  • Gelonin
  • Purging
  • Transplant
  • Peripheral Stem Cell
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



UT MD Anderson Cancer Center Houston, Texas  77030