Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) Initial Salvage Therapy for Induction Failure Acute Myeloid Leukemia (AML)

Salvage Chemotherapy Before Transplant:

Study Drug Administration:

On Days 1-5, you will receive decitabine 1 time each day by vein over about 1-3 hours.

On Days 6-10:

- You will receive cytarabine 1 time a day by vein over about 1-3 hours.

- On Days 6-8 only, you will receive idarubicin 1 time a day by vein over about 30
minutes.

- On Days 6-9 only, you will receive clofarabine 1 time a day by vein over about 1-2
hours.

Study Visits:

After your last study drug dose:

- Blood (about 2 teaspoons) will be drawn to check your kidney and liver function.

- You will have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan to check
your heart function.

- You will have a lung function test.

On Day 21 (+/- 7 days), you will have a bone marrow biopsy/aspirate to check the status of
the disease. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with
anesthetic, and a small amount of bone and bone marrow is withdrawn through a large needle.

If the results of your bone marrow biopsy/aspirate, blood tests, and heart and lung function
tests show that you are eligible to receive an allogeneic stem cell transplant, you will be
asked to sign a separate informed consent for the transplant.

If the results of your bone marrow aspirate/biopsy, blood tests, and heart and lung function
tests show that you are not eligible to receive an allogeneic stem cell transplant you will
not receive it. The study staff will call you and ask how you are feeling and about any other
drugs you may be taking every 3 months for 2 years after your last study drug dose. These
calls should last about 5 minutes each.

If you are found to NOT be eligible to receive an allogeneic stem cell transplant, your
doctor will discuss other treatment options with you.

Stem Cell Transplant:

Study Drug Administration, Pharmacokinetic (PK) Testing, and Stem Cell Transplant:

For a stem cell transplant, the days before you receive your stem cells are called minus
days. The day you receive the stem cells is called Day 0. The days after you receive the stem
cells are called plus days.

You will receive a dose of busulfan by vein over about 45 minutes to 1 hour as an outpatient
or as an inpatient on Day -8. With the first busulfan infusion, blood (about 1 teaspoon each
time) will be drawn for pharmacokinetic (PK) testing about 11 times over 11 hours before and
after you receive your first dose of busulfan. PK testing measures the amount of study drug
in the body at different time points. The study staff will tell you the blood testing
schedule. Test doses are used to study how your body breaks down busulfan and decide the dose
of busulfan that you will receive on Days -6 through -3.

A heparin lock line will be placed in your vein before the PK testing to lower the number of
needle sticks needed for these draws. If for any reason it is not possible for the PK tests
to be performed, you will receive the standard dose of busulfan.

On Day -7, you will rest.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour, clofarabine by vein
over 1 hour, and then busulfan by vein over 3 hours.

On Days -3 and -2, if you will receive stem cells from a matched unrelated donor, you will
receive ATG by vein over 4 hours each day.

On Day -2, if you will receive stem cells from a haploidentical donor, you will receive total
body irradiation (TBI) one time. TBI involves the delivery of high doses of radiation
designed to destroy cancer cells and/or lower the immune system in order to lower the risk of
the body rejecting the new stem cells.

On Day -2, you will receive tacrolimus by vein over 24 hours every day until you are able to
take it by mouth. Tacrolimus is designed to weaken the immune system and lower the risk of
graft-versus-host-disease (GVHD - a reaction of the donor's immune cells against your body).
After you are able to take tacrolimus by mouth, you will take it every day for about 6
months, or until the doctor thinks it is safe to stop.

On Day -1, you will rest. If you will receive stem cells from a matched sibling donor, you
will rest on Days -2 and -1.

On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.

If you will receive stem cells from a haploidentical donor:

After the stem cell infusion, you will receive tacrolimus to help lower the risk of GVHD.
Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2 weeks of taking
tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 4 months after
the transplant.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours. Cyclophosphamide
is given to lower the immune system in order to lower the risk of GVHD.

If you receive stem cells from a matched sibling or matched unrelated donor:

On Days +1, +3, +6, and +11, you will receive methotrexate by vein over 30 minutes.
Methotrexate is given to help prevent GVHD.

Study Testing:

Before you are sent home from the hospital and/or clinic, you will receive additional written
instructions. These instructions will include how often you will come to the hospital/clinic,
which standard drugs you will take at home, and what side effects you may have and what to do
for them.

After finishing the chemotherapy and transplant, your follow-up care will be routine standard
of care follow-up that all patients receiving allogeneic stem cell transplantation receive.
At each visit, you will have a physical exam. You will be asked about any side effects you
may have had. Blood (about 1 tablespoon) will be drawn for routine tests. If the doctor
thinks it is needed, you will have a bone marrow aspiration to check the status of the
disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with
anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Treatment:

After 2 years, your participation in this study will be over. You may be taken off study
early if the disease gets worse, if your transplant does not "take" (graft failure), if you
are unable to follow study directions, if your doctor thinks it is in your best interest, if
the study is stopped, or if you choose to leave the study early.

If for any reason you want to leave the study early, you must talk to the study doctor. It
may be life-threatening to leave the study after you have started to receive the study drugs
but before you receive the stem cell transplant because your blood cell counts will be
dangerously low.

Inclusion Criteria:

1. Patients age 18-60 years.

2. Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML
induction therapy (> 5% blasts on day 21 (+/-7 days) bone marrow aspirate and/or
biopsy from the beginning of induction chemotherapy, up to 42 days).

3. Eastern Cooperative Oncology Group (ECOG) Performance Status
4. Adequate major organ function:, defined as: a) Serum creatinine bilirubin disease; d) Cardiac ejection fraction >/= 40% (by either ECHO or MUGA).

5. Willingness to have an allogeneic transplant.

6. Patient or patient's legal representative able to provide written informed consent.

7. Patients are required to meet the following criteria to proceed to AHSCT:

8. Donor criteria: Availability of a donor either an HLA matched sibling donor (MSD) or a
haploidentical (5-9/10 HLA matched); alternatively a 8/8 HLA matched unrelated donor
(MUD) by high resolution typing is immediately available;

9. Disease criteria: Day 21 (+/-7 days) bone marrow aspiration or biopsy from the
beginning of salvage DCIA: a. In complete morphologic remission with <5% bone marrow
blasts, or b. Aplastic (<10% bone marrow cellularity), and cytopenic with an absolute
neutrophil count (ANC) less than 1,000/µL, or c. Low disease burden with < 30% BM
blasts, with recovery of peripheral blood (PB) WBC (ANC>1,000/µL) and <5% circulating
blasts.

10. Adequate organ function criteria: a. Serum creatinine clearance >/= 50 ml/min
(calculated by Cockcroft-Gault formula); b. Total bilirubin normal (x ULN) (3 x ULN if considered to be due to leukemic involvement or Gilbert's
syndrome); c. Alanine aminotransferase (ALT) be due to leukemic involvement); d. LVEF >/= 40% on ECHO or MUGA; e. DLCO >/= 50%
predicted after correction for hemoglobin (must be performed in patients with history
of smoking or lung disease;); DLCO may be omitted in patients without history of
pulmonary disease if approved by the Study Chair.

11. No active infection: Patients should be afebrile. If present, pulmonary infiltrates or
other sites of infection must be improving on antibiotics. Patients should not require
oxygen. Study Chair will be the arbiter of this criterion.

Exclusion Criteria:

1. HIV positive; active hepatitis B or C.

2. Uncontrolled active infections (viral, bacterial, and fungal); the Study Chair will be
the final arbiter of this criterion.

3. Patients with active secondary malignancy unless approved by the Study Chair.

4. Liver cirrhosis.

5. Active CNS involvement within the previous 2 months.

6. Prior induction therapy with DAC + CIA.

7. Positive pregnancy test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization.

8. Breast feeding women.

9. Men must agree not to father a child and agree to use a condom if his partner is of
child bearing potential.

10. Inability to comply with medical therapy or follow-up.