Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 4 groups of up to 6 participants will be
enrolled in the Phase I portion of the study, and up to 53 participants will be enrolled in
Phase II.

If you are enrolled in the Phase I portion, the dose of Lintuzumab-Ac225 you receive will
depend on when you joined this study. The first group of participants will receive the
lowest dose level of Lintuzumab-Ac225. Each new group will receive a higher dose of
Lintuzumab-Ac225 than the group before it, if no intolerable side effects were seen. This
will continue until the highest tolerable dose of Lintuzumab-Ac225 is found.

If you are enrolled in the Phase II portion, you will receive Lintuzumab-Ac225 at the
highest dose that was tolerated in the Phase I portion.

All participants will receive the same dose level of cytarabine.

Study Drug Administration:

You will receive cytarabine as an injection under the skin. This is called a subcutaneous
injection. During the first office visit, you or a caregiver will be taught to give these
injections at home. You will get cytarabine injections 2 times each day during Days 1-10 of
each study cycle. Cycle 1 may last up to 52 days and will depend on how you recover from
the Lintuzumab-Ac225. All other cycles will be 28 days.

You will receive Lintuzumab-Ac225 by vein over 15-30 minutes at a time point about 4 to 7
days after your last dose of cytarabine in Cycle 1. You will receive it a second time about
4 to 7 days after that.

One (1) day before the second dose of Lintuzumab-Ac225, you will begin taking lasix
(furosemide) by mouth every day for 10 days. Furosemide is taken to prevent possible damage
to the kidneys.

One (1) day after your last dose of furosemide, you will begin taking spironolactone by
mouth every day for up to 1 year. It is also taken to prevent possible kidney damage.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Study Visits:

During Cycle 1:

- Every week, blood (6-10 teaspoons) will be drawn for routine tests.

- Every other week, urine will be collected for routine tests.

- About 1 week before Cycle 2, you will have a bone marrow aspirate and biopsy to check
the status of the disease.

During Cycles 2-12:

- Every week, blood (6-10 teaspoons) will be drawn for routine tests.

- Blood (about 1-2 teaspoons) will be drawn to find out how Lintuzumab-Ac225 may affect
your immune system (Cycles 3, 4, and 7 only).

- Every month, urine will be collected for routine tests.

- About 1 week before Cycles 3 and 5, you will have a bone marrow aspirate and biopsy to
check the status of the disease.

Length of Study:

You will only receive Lintuzumab-Ac225 during the first cycle, but you may continue
receiving cytarabine for up to 12 cycles. You will be taken off the study if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

Your participation on the study will be over once you have completed the follow-up.

If you stop taking the study drugs before all 12 treatment cycles are finished, you may be
contacted by telephone or be seen in the clinic every month for up to 1 year to check on any
side effects you may be having.

This is an investigational study. Lintuzumab-Ac225 is not FDA approved or commercially
available. It is currently being used for research purposes only. Cytarabine is FDA approved
and commercially available for the treatment of AML. The use of these drugs in combination
for AML is investigational.

Up to 72 participants will be enrolled in this multicenter study. Up to 24 will take part
at MD Anderson.

Inclusion Criteria:

1. Untreated AML, including patients with an antecedent hematologic disorder or
secondary disease. Patients with prior MDS may have received therapy with
immunomodulatory agents or hypomethylating agents for this diagnosis. patients with
other prior cancer diagnoses are allowed as long as they ahve no measurable disease
are not undergoing active therapy, and have a life expectancy of greater than or
equal 4 months.

2. Patients age greater than or equal to 60 years who: a. Are unwilling to receive
intensive (e.g. 7+3) chemotherapy, or b. Have poor-risk prognostic factors defined as
antecedent hematologic disorder, prior chemotherapy or XRT, abnormal karyotype other
than t(8;21), inv16, or t(16;16), any karyotype with FLT3-ITD, or presenting WBC
greater than 100K, or c. Have significant comorbidities, that in the judgment of the
investigator makes the subject unsuitable for standard dose induction chemotherapy
(e.g. anthracycline and infusional cytarabine given as 7+3); or d. Any patient age
greater than or equal to 70 years.

3. Blast count greater than or equal to 20 percent (WHO criteria)

4. Greater than 25 percent of blasts must be CD33 positive.

5. Creatinine less than 2.0 mg/dl

6. Estimated creatinine clearance greater than or equal to 50ml/min.

7. Bilirubin less than or equal to 2.0 mg/dl; AST and ALT less than or equal to 2.5
times the ULN.

8. ECOG Performance status less than or equal to 3.

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia.

2. Treatment with chemotherapy or biologic therapy within 3 weeks, except for
hydroxyurea, which must be discontinued prior to treatment on study

3. Treatment with radiation within 6 weeks

4. Active serious infections uncontrolled by antibiotics

5. Active malignancy within 2 years of entry, except previously treated non-melanoma
skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ
confined prostate cancer with no evidence of progressive disease based on PSA levels
and are not on active therapy

6. Clinically significant cardiac or pulmonary disease

7. Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those
with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to
exclude CNS disease. Symptoms include cranial neuropathies, other neurologic
deficits, and headache.

8. Psychiatric disorder that would preclude study participation.