Phase I/II - Brentuximab/5-Azacytidine in Acute Myeloid Leukemia (AML)

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 3 groups of 3-6 participants will be enrolled
in the Pilot Phase, up to 3 groups of 3-6 participants will be enrolled in Phase I of the
study, and up to 25 participants will be enrolled in Phase II.

If you are enrolled in the Pilot Phase, the dose of brentuximab vedotin you receive will
depend on when you joined this study. The first group of participants will receive the
highest dose level of brentuximab vedotin. If intolerable side effects are seen, up to 2
more groups will be enrolled and will receive a lower dose of brentuximab vedotin than the
group before it. If intolerable side effects are not seen, the next phase of the study will
begin.

If you are enrolled in Phase I, the dose of brentuximab vedotin you receive will depend on
when you joined this study. The first group of participants will receive a lower dose level
of brentuximab vedotin than the highest one that was tolerated in the Pilot Phase, and will
also receive azacitidine. If intolerable side effects are seen, up to 2 more groups will be
enrolled and will receive a lower dose of brentuximab vedotin than the group before it. If
intolerable side effects are not seen, the next phase of the study will begin.

If you are enrolled in Phase 2, you will receive brentuximab vedotin at the highest dose
that was tolerated in Phase 1.

All participants in Phases 1 and 2 will receive the same dose level of azacytidine.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive brentuximab
vedotin by vein over 30 minutes on Days 1, 8, and 15 of each 28-day study cycle. If the
disease appears to get better, or after cycle 4, the dose and schedule of brentuximab
vedotin may be changed to monthly rather than weekly doses.

If you are in Phase 1 or Phase 2, you will also receive azacytidine by vein or as an
injection under the skin on Days 1-7 of each cycle.

You may 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:

On Day 1 of each cycle:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine tests.

- You will have an EKG.

- Every 3 Cycles (Cycles 3, 6, 9, and so on), if you can become pregnant, blood (about 1
teaspoon) or urine will be collected for a pregnancy test.

On Days 8 and 22 of Cycle 1, blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 15 of Cycle 1:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 28 of Cycle 1, then Day 1 of every 2 cycles after that (Cycles 3, 5, 7, and so on),
you will have a bone marrow biopsy and/or aspirate to check the status of the disease. After
any point that the disease appears to get better, this will be done every 3-4 cycles, or
whenever your doctor thinks it is needed.

Length of Treatment:

You may receive the study drug for up to 12 cycles. You will no longer be able to receive
the study drug(s) 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 after the end-of-study visit.

End-of-Study Visit:

About 28 days after your last dose of study drug, you will have an end-of-study visit:

- You will have a physical exam.

- Blood (about 2-3 tablespoons) will be drawn for routine tests.

- You will have an EKG to check your heart function.

- You may have a bone marrow biopsy and/or aspirate to check the status of the disease.

- If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a
pregnancy test.

If the End-of-Study Visit occurs within 21 days of your last dose, you will be called by a
member of the study team about 30-37 days after your last dose of study drug. You will be
asked how you are feeling and about any side effects you may be having. This call will last
about 5 minutes.

This is an investigational study. Brentuximab vedotin is FDA approved and commercially
available for the treatment of certain types of lymphoma after previous treatments have
failed. Its use in combination with azacitidine is investigational. Azacytidine is FDA
approved and commercially available for the treatment of myelodysplastic syndrome (MDS) and
chronic myelomonocytic leukemia (CMML).

The study doctor can explain how the study drug(s) are designed to work.

Up to 61 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Histologically or cytologically confirmed AML, other than acute promyelocytic
leukemia, as defined by the 2008 World Health Organization (WHO) criteria that is
relapsed or refractory to standard chemotherapy. Note: Newly-diagnosed AML patients
who are 60 years or older and are not candidates for or have refused standard
chemotherapy are also eligible for this trial.

2. AML blasts must express CD30 (>/=10% expression as assessed by flow-cytometry or 2+
expression by immunohistochemistry) (whenever possible CD30 expression will be
assessed by both methods)

3. Age 18 years or older

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of
5. The following baseline laboratory data: Serum bilirubin normal (ULN) or 30 ml/min; Alanine aminotransferase (ALT) and
aspartate aminotransferase (AST)
6. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the
first dose of brentuximab vedotin and must agree to use an effective contraception
method during the study and for 30 days following the last dose of study drug.
Females of non- childbearing potential are those who are postmenopausal greater than
1 year or who have had a bilateral tubal ligation or hysterectomy.

7. Males who have partners of childbearing potential must agree to use an effective
contraceptive method during the study and for 30 days following the last dose of
study drug

8. Patients or their legally authorized representative must provide written informed
consent.

Exclusion Criteria:

1. History of another primary invasive malignancy that has not been definitively treated
or in remission for at least 2 years. Patients with non-melanoma skin cancers or with
carcinomas in situ are eligible regardless of the time from diagnosis (including
concomitant diagnoses).

2. Documented history of a cerebral vascular event (stroke or transient ischemic
attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with
New York Heart Association Class III-IV within 6 months prior to their first dose of
brentuximab vedotin

3. Evidence of active cerebral/meningeal disease. Patients may have history of CNS
leukemic involvement if definitively treated with prior therapy and no evidence of
active disease at the time of registration.

4. Previous treatment with any anti-CD30 directed therapy

5. Patients with previous allogeneic stem cell transplant (SCT) if they meet either of
the following criteria: <100 days from allogeneic SCT, Acute or chronic
graft-versus-host disease (GvHD), or Receiving immunosuppressive therapy as treatment
for or prophylaxis against GvHD within the last 7 days

6. Patients with uncontrolled active infections (viral, bacterial, and fungal) are not
eligible.

7. Known to be positive for hepatitis B by surface antigen expression

8. Known to have active hepatitis C infection (positive by polymerase chain reaction or
on antiviral therapy for hepatitis C within the last 6 months)

9. Preexisting grade >/=2 peripheral neuropathy

10. Patients with uncontrolled diabetes mellitus

11. Current therapy with other systemic anti-neoplastic or anti-neoplastic
investigational agents.

12. Chemotherapy (except hydroxyurea or emergent use of single-agent cytarabine for
cytoreduction), radiotherapy, biologics, and/or other treatment with immunotherapy
that is not completed 2 weeks prior to first dose of study drug, unless progressive
disease is documented. NOTE: Hydroxyurea will be allowed during the first cycle of
treatment

13. Females who are pregnant or lactating

14. Known hypersensitivity to any excipient contained in the drug formulation of
brentuximab vedotin

15. History of progressive multifocal leukoencephalopathy (PML)