Trial Information

A Prospective Randomized Phase I/II Study of Clofarabine (Clo) and Ara-C vs Clo and Ida vs Clo Plus Ida and Ara-C in Patients With First Relapse or First Salvage of Primary Refractory AML; and High-Grade MDS(>/= 10% Blasts); or CML in Myeloid Blasts Phase as Front Line Therapy or in First Salvage.

Clofarabine is a new drug that was designed to help treat leukemia. Ara-C and idarubicin are
drugs that are commonly used to help treat leukemia.

Before treatment starts, you will be asked questions about your medical history and have a
complete physical exam. You will have blood samples (about 1 tablespoon) collected for
routine lab tests. You will either have an echocardiogram or a MUGA scan to check on the
function of your heart. You will have a sample of bone marrow collected to check on the
status of the disease. To collect a bone marrow sample, an area of the hip or chest bone is
numbed with anesthetic and a small amount of bone marrow is withdrawn through a large
needle. Women who are able to have children must have a negative blood or urine pregnancy
test.

The first group of participants entering the study will take part in the Phase I portion of
the study. The goal of the Phase I portion is to find the best safe dose for the drug
combinations clofarabine plus idarubicin and clofarabine plus idarubicin and ara-C. If you
are taking part in the Phase I portion of this study, you will be assigned to one of two
groups. Participants in the first group will receive the combination of clofarabine and
idarubicin. Participants in the second group will receive the combination of clofarabine,
idarubicin, and ara-C.

For participants in the clofarabine/idarubicin group, the clofarabine will be given by vein
over 1 hour once a day for 5 days in a row. Idarubicin is given by vein over 30 minutes,
around one hour after clofarabine, for the first 3 days. This 5 day period is called a
cycle of chemotherapy.

For participants in the clofarabine/idarubicin/ara-C group, the clofarabine will be given
by vein over 1 hour once a day for 5 days in a row, on Days 2 to 6 of each cycle.
Idarubicin will be given by vein over 30 minutes for 3 days in a row, on Days 1 to 3 of each
cycle. Ara-C will be given by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each
cycle. Idarubicin is usually started around 1 hour after the completion of clofarabine, and
ara-C about 4 hours after the start of the clofarabine infusion. This 6 day period is
called a cycle of chemotherapy.

For participants in both groups, after each cycle of therapy, you will not receive the next
cycle of chemotherapy until your blood counts have recovered and any possible side effects
have gone away (for around 3 to 6 weeks). If the disease gets worse or side effects become
too severe, treatment will stop. You must stay in Houston for the first 4 to 6 weeks
(average) of treatment and are required to return to Houston to receive each additional
cycle of chemotherapy (up to 6 days each cycle).

The first few participants entering the Phase I portion of the study will receive a low dose
of the study drugs. The next few participants will receive a slightly higher dose of the
drugs. This will continue until the best safe dose for the 2 combinations of drugs are
found.

If you are taking part in the Phase I portion of the study, you will receive at least 1
cycle of therapy. If after 1-2 cycles of therapy it is found that the disease is responding
to therapy, you may continue to receive therapy for up to 4 additional courses of
"consolidation therapy". During the "consolidation therapy" you will also be given
treatment courses with ara-C alone. When ara-C is given alone it will be given as a
continuous infusion, 24 hours a day, for 5 days in a row. You will be given a portable pump
so that this treatment can be done as an outpatient. The combination drug courses and the
ara-C courses will alternate (ara-C alone, combination, ara-C alone, combination) for a
total of 4 courses. If it is found that the disease is not responding to chemotherapy, you
will be taken off the study and your doctor will discuss other treatment options with you.

Once the best safe dose of these drug combinations are found, the next group of participants
entering the study will take part in the Phase II portion of the study. The goal of this
part of the study is to compare the effects of the drug combinations of
clofarabine/idarubicin/ara-C, clofarabine/ara-C, and clofarabine/idarubicin in the treatment
of AML, MDS, and CML.

If you are taking part in the Phase II portion of the study, you will be assigned to receive
treatment with clofarabine plus idarubicin and ara-C.

For participants in the clofarabine/idarubicin/ara-C group, the clofarabine will be given
by vein over 1 hour once a day for 5 days in a row, on Days 2 to 6 of each cycle.
Idarubicin will be given by vein over 30 minutes for 3 days in a row, on Days 1 to 3 of each
cycle. Ara-C will be given by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each
cycle. Idarubicin is usually started around 1 hour after the completion of clofarabine, and
ara-C about 4 hours after the start of the clofarabine infusion. This 6 day period is
called a cycle of chemotherapy.

If you are taking part in the Phase II portion of the study, you will receive at least 1
cycle of therapy. If after 1 or 2 cycles of therapy it is found that the disease is
responding to therapy, you may continue to receive therapy for up to 4 additional courses of
"consolidation therapy". During the "consolidation therapy" you will also be given
treatment courses with ara-C alone. When ara-C is given alone it will be given as a
continuous infusion, 24 hours a day, for 5 days in a row. You will be given a portable pump
so that this treatment can be done as an outpatient. The combination drug courses and the
ara-C courses will alternate (ara-C alone, combination, ara-C alone, combination) for a
total of 4 courses. If it is found that the disease is not responding to chemotherapy, you
will be taken off the study and your doctor will discuss other treatment options with you.

The check-up visits will be the same for the participants in the Phase I and Phase II
portions of the study. Before you receive each dose of drug(s), you will have a complete
physical exam. During treatment, you will have blood (about 1 tablespoon) collected at
least once a week during the first 2 courses of therapy, then every 2-4 weeks after. Bone
marrow samples will be collected every other week during treatment to check on the status of
the disease. The blood and bone marrow samples may be collected more often if your doctor
feels it is necessary.

If, at any time, the disease gets worse or you experience any intolerable side effects, you
will be taken off the study and your doctor will discuss other treatment options with you.

After your last course of treatment, you will have a follow-up visit scheduled. At this
visit, you will have blood (about 1 tablespoon) collected for routine tests. You will have
a sample of bone marrow collected to check on the status of the disease. You will also have
a repeat echocardiogram or MUGA scan to check on the function of your heart.

This is an investigational study. Clofarabine has been authorized by the FDA to be used in
research only. Idarubicin and ara-C are both FDA approved and are commercially available. A
total of 44 patients were enrolled in the Phase I part of the study, which is now complete.
Up to 120 participants will take part in the phase II part of this study. All will be
enrolled at M. D. Anderson.