Trial Information

Phase 2 Study of Planned Donor Lymphocyte Infusion After Reduced Intensity Allogeneic Stem Cell Transplantation

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the flip of a
coin) to 1 of 2 study groups involving the dose of T-cells in the donor lymphocyte infusion.

- Group 1 will receive a low dose of donor T-cells.

- Group 2 will receive a higher dose of donor T-cells than Group 1.

Both you and your study doctor will know which group you are in. Both groups will have a
stem cell transplant. The stem cells will be given by vein. The cells will travel to your
bone marrow where they are designed to make healthy, new blood cells after several weeks.

Study Drug Administration:

Patients receive fludarabine, melphalan and alemtuzumab to kill malignant cells and suppress
immunity to prevent rejection of the stem cell transplant. The day you receive the stem
cells is called Day 0. The days before you receive your stem cells are called minus days.
The days after you receive the stem cells are called plus days.

On Day -7, you will be admitted to the hospital and given fluids by vein to hydrate you.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour each day.

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

On Day -1, you will receive alemtuzumab by vein over 2 hours.

On Day 0, you will receive the stem cell transplant as a cell infusion by vein.

After the transplant, you will receive tacrolimus and methotrexate. At first, you will
receive tacrolimus as a continuous (nonstop) infusion until you are able to take it by
mouth. You will then take tacrolimus by mouth 2 times a day for about 5 weeks and then your
doctor will tell you how to taper it off (gradually stop taking it). On Days 1, 3, and 6
after the transplant, you will receive methotrexate by vein over 30 minutes.

You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week
after the transplant, until your blood cell levels return to normal. Filgrastim is designed
to help with the growth of white blood cells.

Between Day +56 and +64, if you are in stable medical condition and have not developed GvHD,
you will receive a donor lymphocyte infusion containing T-cells by vein over 10-30 minutes.
You will receive Benadryl (diphenhydramine) by vein over 15 minutes before the infusion to
lower the risk of an allergic reaction.

Study Visits:

Before the T-cell infusion:

- You will have a physical exam, including measurement of your vital signs (blood
pressure, heart rate, temperature, and breathing rate).

- You will be asked about how you are feeling and about any side effects you may be
having.

- Blood (about 2 teaspoons) will be drawn to see how well the transplant has "taken".

- You will have a bone marrow aspiration and biopsy to check the status of the disease,
if your doctor thinks it is needed. To collect a bone marrow aspiration/biopsy, an
area of the hip or other site is numbed with anesthetic, and a small amount of bone
marrow and bone is withdrawn through a large needle.

After the T-cell infusion, you will have a physical exam every week for at least 6 weeks.

About 3, 6, and 12 months after the transplant:

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

- You will be asked about how you are feeling and about any side effects you may be
having.

- Blood (about 4 tablespoons) will be drawn for routine tests and to check the level of
the infused T-cells, for immune function tests, and to check the status of the disease.

- You will have a bone marrow aspiration, blood tests and CT scans as medically necessary
to check the status of the disease, if your doctor thinks it is needed.

During the study, you will have blood draws (about 2 teaspoons) and urine will be collected
for routine tests, to check your blood counts, kidney and liver function, and/or to check
for infections as often as the doctor thinks is needed during this time.

Length of Treatment:

You will be off study after your 12-month follow-up visit. You will be taken off study
early if you have graft failure (the donor cells did not "take") or if the cancer comes back
and needs another treatment.

This is an investigational study. Melphalan, fludarabine, and alemtuzumab are FDA approved
and commercially available for the treatment of blood cancers. Donor T-cell infusions are
commonly used to treat blood cancers that come back after a stem cell transplant. The
investigational part of this study is to find the best dose of T-cells that are given with
the goal of helping to prevent the cancer from coming back.

Up to 56 patients will take part in this study. All will be enrolled at MD Anderson.