Leukemia SPORE Phase II Randomized Study of Decitabine Versus Decitabine and Carboplatin Versus Decitabine and Arsenic in Relapsed, Refractory, and Elderly AML and MDS

Study Groups:

If you are found to be eligible to take part in this study and you are one of the first 30
participants enrolled, you will have an equal chance of being in one of 3 study groups. If
you enroll after the first 30 participants are enrolled, you will have a higher chance of
being assigned to the group is having better results.

- If you are in Group 1, you will receive decitabine alone.

- If you are in Group 2, you will receive decitabine and carboplatin.

- If you are in Group 3, you will receive decitabine and arsenic trioxide.

Study Drug Administration:

Every 4 weeks is a study cycle.

You will receive decitabine by vein over about 1 hours on Days 1-5 of each cycle.

If you are receiving carboplatin, you will receive it over 1 hour on Day 8 (+/-2 days) of
each cycle.

If you are receiving arsenic trioxide, you will receive it over about 1 hour on Days 1-5 of
each cycle

Study Visits:

Blood (about 1-2 teaspoons) will be drawn 1-2 times a week during Cycle 1 and then every 2-4
weeks after that for routine tests. If you have stable disease, blood will only be drawn
every 4-6 weeks.

On Day 28 of Cycle 3 (+/- 3 days), you will have a bone marrow aspirate and biopsy to check
the status of the disease. After that, you will have bone marrow biopsies/aspirations when
the doctor thinks it is needed.

If you are in Group 3, you will have EKGs on Day 1 of each cycle before receiving the study
drugs. On Days 1 and 4 of each cycle, blood (about 1-2 teaspoons) will also be drawn for
routine tests before your dose of the study drugs.

If you are taken off study, blood (about 1-2 teaspoons) will be drawn for routine tests.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug(s) if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Arsenic trioxide is FDA approved and commercially
available for the treatment of APL. Decitabine is FDA approved and commercially available
for the treatment of MDS. Carboplatin is FDA approved and commercially available for the
treatment solid tumors. The study drug or study drug combination you receive on this study
are considered investigational.

Inclusion Criteria:

1. Patients with AML, relapsed or refractory to standard therapy or elderly patients
with AML (age 65 or over). Patients who have AML and are younger than age 65 but
considered unfit for conventional chemotherapy are eligible. Patients with de novo or
treated MDS or CMML INT-1 or above are eligible. Patients may have had prior exposure
to azacitidine but no more than one cycle of decitabine. Patients must have been off
chemotherapy for 2 weeks prior to entering this study and have recovered from the
toxicities of that therapy; A caveat to this is in the case of rapidly progressive
disease. Hydroxyurea is permitted for control of elevated WBC prior to treatment and
can be continued for the first 4 weeks of therapy. Erythropoiesis stimulating agents
(ESAs) and GCSF are allowed before therapy. ESAs, GCSF or other growth factors are
permitted on therapy.

2. Performance 0-2 (ECOG).

3. Adequate cardiac functions assessed by 2D ECHO (NYHA cardiac III-IV excluded).

4. Pre-treatment EKG

5. Adequate end organ function with creatinine 2mg/dL, AST and ALT
6. Absence of significant intercurrent illness such as uncontrolled heart failure,
unstable angina, cardiac arrhythmia and psychiatric illness which precludes the
giving of informed consent.

7. Signed informed consent

Exclusion Criteria:

1. Nursing and pregnant females. Patients of childbearing potential should practice
effective methods of contraception. Should a woman become preg-nant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately.

2. Current uncontrolled infections.

3. Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, or psychiatric illness/social
situations that would limit compliance with study requirements.

4. Chronic kidney disease > stage 3.

5. HIV infection.