Evaluation of Safety and Efficacy of TXA127 to Enhance Engraftment in Adults Undergoing Double Cord Blood Transplantation Transplant

The Study Drugs and Transplant:

TXA127 is designed to increase the growth of certain types of cells, especially those cells
that grow into mature blood cells such as platelets. Researchers want to learn if TXA127
can help your blood cell counts to recover faster after chemotherapy and a cord blood
transplant.

The chemotherapy in this study includes fludarabine and melphalan with or without thiotepa.
All 3 of these drugs are designed to damage the DNA (genetic material) of cells, which may
cause cancer cells to die.

A cord blood transplant is the use of stem cells (blood-forming cells) from the umbilical
cord that are infused into a patient's body to replace damaged bone marrow. Since the
number of stem cells in 1 cord blood "unit" (amount) is small, participants will receive 2
units. This is called a "double" cord blood transplant, and it may help the transplant to
work faster.

Study Plan:

If you are found to be eligible to take part in this study, you will follow the steps
described below:

- placement of a central venous catheter (CVC)

- collection of back-up stem cells

- selection of an alternate back-up donor

- chemotherapy

- cord blood transplant

- study drug (TXA127) administration

- drugs after the transplant to lower the risk of graft-versus-host disease (GVHD -- a
disease that occurs when transplanted immune tissue (such as stem cells) attacks the
tissue of the recipient's body)

CVC Placement:

First you will receive a central venous catheter (CVC) that will be used to draw blood and
to give some of the drugs by vein. A CVC is a sterile flexible tube that will be placed
into a large vein while you are under local anesthesia. Your doctor will explain this
procedure to you in more detail, and you will be required to sign a separate consent form
for this procedure.

Back-up Stem Cell Collection:

A back-up sample of your stem cells will be collected using one of the procedures described
below. This sample will only be used later if the doctors think it is needed to help your
bone marrow function recover.

If your back-up stem cells will be collected from your peripheral (circulating) blood, then
a sample of blood cells called peripheral blood progenitor cells (PBPCs) will be collected
from your CVC during a procedure called leukapheresis. Leukapheresis involves separating
some of your blood cells from your whole blood. The procedure involves drawing blood that is
passed through a blood cell separator (a machine designed for collecting different parts of
the blood).

The leukapheresis procedure is done in the outpatient clinic and takes about 3-4 hours. In
the week before your PBPCs are collected, you will receive granulocyte colony stimulating
factor (G-CSF, also known as filgrastim). Filgrastim is designed to cause stem cells in the
bone marrow to move to the peripheral blood so the stem cells can be collected. Filgrastim
will be given by injection under your skin 1 time a day for 3-7 days.

If the leukapheresis cannot be performed successfully, you will receive general anesthesia
in the operating room and will have multiple needle sticks of the hip bones in order to
collect a back-up sample of bone marrow. You will be required to sign a separate consent
form for this procedure, if done.

Selection of Alternate Back-up Donor:

If your own back-up stem cells cannot be collected, a family member will be asked to serve
as a back-up donor or back-up cord blood will be used. M. D. Anderson will receive 3 units
of blood. If needed, the third unit will be used. A back-up donor or third cord blood unit
will be required for you to take part in this research study.

Chemotherapy:

Your bone marrow transplant doctors will assign you to 1 of 2 study groups. This decision
will be made based on what the doctors think is best for someone with your health status and
the disease status.

- Group 1 will receive fludarabine, thiotepa, and melphalan.

- Group 2 will receive fludarabine and melphalan.

Group 1 will receive chemotherapy on the following schedule:

- On Day -8 (8 days before the cord blood infusion and TXA127 dose), you will receive
melphalan by vein over at least 30 minutes.

- On Day -7, you will receive thiotepa by vein over at least 4 hours.

- One (1) time a day from Day -6 through Day -3, you will receive fludarabine by vein
over at least 1 hour. On Days -4 and -3, you will also receive antithymocyte globulin
(ATG) by vein over at least 4 hours. ATG is a chemotherapy drug that is also given to
lower the risk of GVHD.

Group 2 will receive chemotherapy on the following schedule:

- One (1) time a day from Day -5 through Day -2, you will receive fludarabine by vein
over at least 1 hour.

- On Days -3 and -2, you will also receive ATG by vein over at least 4 hours.

- On Day -2, you will receive melphalan by vein over at least 30 minutes.

Transplant:

You will receive the cord blood transplant on Day 0. The cord blood will be given by vein
through your CVC over about 30 minutes.

Study Drug Administration:

Also on Day 0, you will begin receiving TXA127 as an injection under your skin 1 time a day
for up to 28 days. The injections will stop early if your blood platelet count stays at a
certain level for more than 3 days.

Drugs to Prevent GVHD:

You will stay in the hospital until your bone marrow function is restored enough after the
transplant. This usually takes about 3-6 weeks. During this time, you will receive drugs,
blood transfusions, and other standard procedures that are designed to lower the risks of
the transplant (such as GVHD).

You will receive mycophenolate mofetil and tacrolimus to lower the risk of GVHD:

- Mycophenolate mofetil will be given by mouth 2 times a day (morning and evening) on Day
-3 through Day 100.

- Tacrolimus will be given through your CVC continuously (non-stop) for about 3-6 weeks
(until your blood platelet count stays at a certain level for 3 days in a row). After
that, you will start taking tacrolimus pills by mouth 1 time a day for 180 days (6
months). The number of tacrolimus pills is different from person to person, but it is
usually between 1-5 pills. Your doctor may decide to gradually lower your dose of
tacrolimus around Day 180 if you do not develop GVHD. You may continue taking
tacrolimus for about another 3 months or possibly longer if you develop chronic GVHD.

Study Visits:

Every day from Day -8 through Day 27 (+/- 1 day):

- Your vital signs will be measured.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any side effects you may have had and any changes in the drugs
you may be taking.

On Day 0 only:

- Your height will be measured.

- If you are able to become pregnant, you will have a blood (about 1 tablespoon)
pregnancy test.

Every day from Day 0 through Day 27 (+/- 1 day):

- Your vital signs will be measured.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have a mouth exam to check for sores and/or inflammation.

- You will be asked about any side effects you may have had and any changes in the drugs
you may be taking.

On Days 0, 6, 13, 20, and 27 (+/- 1 day), the following tests and procedures will also be
performed:

- Blood (about 3 tablespoons) and urine will be collected for routine tests. In Week 1
(Days 0 and 6), this blood will also be used to check your blood clotting function.

- You will have a physical exam, including measurement of your weight. As part of the
physical exam, the doctor will check for symptoms of GVHD such as skin rash.

- Your performance status will be recorded.

- You will be asked about any side effects you may have had and any changes in the drugs
you may be taking.

On Day 30, blood (about 2 tablespoons) will be drawn for immune function tests.

Length of Study:

You may continue following the study plan if the doctor thinks it is in your best interest.
You will be taken off study early if the disease gets worse or intolerable side effects
occur. Your participation on the study will be over once you have completed the follow-up
visits and end-of-study visit.

Follow-Up:

One (1) time a week starting 1 week after your last dose of TXA127, until Day 100, the
following tests and procedures will be performed:

- Blood (about 1-2 tablespoons) and urine will be collected for routine tests.

- You will have a physical exam, including measurement of your weight. As part of the
physical exam, the doctor will check for symptoms of GVHD.

- Your performance status will be recorded.

- You will be asked about any side effects you may have had and any changes in the drugs
you may be taking.

On Days 60 and 100, blood (about 2 tablespoons) will be drawn for immune function tests.

On Day 60, you will also have a bone marrow biopsy to check the status of the disease.

End-of-Study Visit:

Within a week after your Day 100 visit (or earlier if you stop the study early), the
following tests and procedures will be performed:

- Blood (about 6 tablespoons) will be drawn for routine tests, blood clotting tests, and
immune function tests.

- Urine will be collected for routine tests.

- You will have a physical exam, including measurement of your weight and vital signs.

- You will have a mouth exam to check for sores and/or inflammation.

- Your performance status will be recorded.

- You will be asked about any side effects you may have had and any changes in the drugs
you may be taking.

- You will have an ECG.

This is an investigational study. TXA127 is not FDA approved or commercially available. It
is currently being used for research purposes only. The chemotherapy in this study is FDA
approved and commercially available. However, the combination of TXA127, a double cord
blood transplant, and chemotherapy is investigational.

Up to 10 patients will take part in this multicenter study. Up to 10 will be enrolled at M.
D. Anderson.