Trial Information

Phase II Study of Fludarabine and Mitoxantrone, Followed by GM-CSF(Granulocyte-macrophage Colony-stimulating Factor) and Rituximab in Patients With Low Grade Non-Hodgkins Lymphoma: An Analysis of Efficacy and Tolerability

Patients with a low-grade, or indolent (slow-growing) form of non-Hodgkin's lymphoma (NHL)
in which the usual survival is between 7-10 years are being asked to take part in this
study. Although normally-used combinations of chemotherapy will cause NHL to disappear in
30-40% of patients (called complete response or complete remission), almost all will have
their disease return.

When NHL is diagnosed, an abundance of white blood cells called B-lymphocytes (or B-cells)
are found in the body. Almost all B-cells have a special protein on the surface called a
CD20 antigen. Some anti-cancer drugs, called monoclonal antibodies, target cancer cells by
binding, or "locking up", specific antigens found on their surfaces, which kills the cancer
cells.

In this study, researchers will test a combination of anti-cancer agents to see if a better
and more long-lasting response can be achieved. All of the medications are approved by the
Food and Drug Administration (FDA) and are available on the market. The agents we will use
are:

-Mitoxantrone and fludarabine, a combination of chemotherapy drugs that has been
successfully used to treat NHL that has returned after treatment.

OR

- Cyclophosphamide and fludarabine, a combination of chemotherapy drugs that has been
successfully used to treat NHL that has returned after treatment.

- Rituximab, a monoclonal antibody that kills cancer cells by binding the CD20 antigen
found on the surface of B-cells, commonly used along with chemotherapy drugs to improve
response rates in lymphoma treatment.

- GM-CSF (granulocyte-macrophage colony stimulating factor, also called sargramostim, GM,
or Leukine), a growth factor which stimulates the development of new (stem) cells.
GM-CSF encourages stem cells to divide, specialize, and become active. It is not a
normal part of treatment for NHL.

Using GM-CSF in NHL treatment is the experimental part of this study. In studies done in
the laboratory, GM-CSF caused an increase in the number of antigens, such as CD20, on the
surface of B-cells. If more antigens are present, it may be easier to target cells that
express CD20 or other antigens. Monoclonal antibodies (such as rituximab) might then be
able to more effectively bind the antigens and kill the cancer cells.

The main purpose of this study is to see if giving GM-CSF along with a standard anti-cancer
treatment will work better to reduce cancer, and to look at side effects of the treatment.