Trial Information

Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies

An autologous transplant uses the recipient's own stem cells, from the blood and bone
marrow, for infusion.

VNP40101M is a chemotherapy drug designed to interfere with the growth and development of
cancer cells, by binding to structures within cancer cells. This drug, given in higher
doses, causes lowering of blood cells. Chemotherapy is commonly given to patients before a
stem cell transplantation to help kill more cancer cells. After receiving this drug, stem
cells are transfused (given gradually) to allow re-growth of the blood cells.

Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in this
study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a
physical exam, including measurement of your vital signs (blood pressure, heart rate,
temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone
marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small
amount of marrow and bone is withdrawn through a large needle. You will have a chest x-ray
and computed tomography (CT) and positron emission tomography (PET) scans, if required, to
measure your tumor. You will have a lung function test and an electrocardiogram (ECG—a test
to measure the electrical activity of the heart). Women who are able to have children must
have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it
will be done with routine blood tests.

Before you receive treatment on this study, you will have apheresis done to collect some of
your stem cells. Apheresis is the process of removing part of the blood (such as platelets
or white blood cells) from the body in order to remove certain elements, such as stem cells.
Then the rest of the blood is returned back to the body. Your stem cells will be put back in
your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein
through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible
tube that will be placed into a large vein while you are under local anesthesia. The details
of apheresis as well as the CVC will be described in separate consent forms. Your doctor
will explain these procedures to you in more detail, and you will be required to sign a
separate consent form for each procedure.

If you are found to be eligible to take part in this study, you will receive a dose of
VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose
that you receive will remain the same throughout this study. Researchers will continue to
enroll patients at the next highest dose level until the highest tolerable dose is found.

About 1 week after your stem cells are collected, you will be admitted to the hospital. You
will stay in the hospital for about 3 weeks. You will then receive VNP40101M by a CVC over 6
hours.

Two days after you receive VNP40101M, the autologous stem cells (blood or bone marrow) will
then be given to you by your CVC. You will receive G-CSF as an injection just under your
skin daily, starting 1 week after your transplantation, which will help your blood cell
levels return to normal.

You will then have blood drawn (about 5 tablespoons) for PK testing to measure the levels of
VNP40101M in your blood. These samples will be drawn through a heparin lock, which will be
in place for 24 hours after the study treatment is complete. A heparin lock is a small tube
connected to a CVC in a vein in the arm for easy access. The heparin lock will be removed
after these samples are received.

After you are released from the hospital, you will be required to stay in the Houston area
for up to 1 month after the transplantation or until you are no longer experiencing any
intolerable side effects. You will be asked to return to M. D. Anderson between 2-4 months
following transplantation so that any late side effects of the study drug can be observed.

As part of standard care, you will have blood tests (about 3 tablespoons) for routine tests.
Your health status will be followed-up to continue to check on the status of the disease.
You will have a computed tomography scan and PET scan. You will also have a bone marrow
biopsy.

If the disease gets worse or you experience any intolerable side effects, you will be taken
off this study.

THIS IS AN INVESTIGATIONAL STUDY. VNP40101M is not FDA approved or commercially available.
It is authorized for use in research only.

Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.