Brentuximab Vedotin + Re-induction Chemotherapy for AML

If patients agree to participate in this research study they will be asked to undergo some
screening tests or procedures to determine eligibility. Many of these tests and procedures
are likely to be part of regular cancer care and may be done even if it turns out that
patients do not take part in the research study. If patients have had some of these tests or
procedures recently, they may or may not have to be repeated. These tests and procedures will
include: a medical history, physical exam, performance status, pregnancy test, urine test,
electrocardiogram, echocardiogram, blood tests, and bone marrow aspirate/biopsy. If these
tests show that patients are eligible to participate in the research study, they will begin
the study treatment. If patients do not meet the eligibility criteria, they will not be able
to participate in this research study.

To start re-induction therapy, patients will receive brentuximab vedotin alone on Day 1. They
will begin treatment with MEC (mitoxantrone, etoposide and cytarabine) a few days later (on
Day 3). Since investigators are looking for the highest dose at which brentuximab vedotin can
be safely administered with MEC without severe or unmanageable side effects in those with
AML, not everyone who participates in this research study will receive the same dose of the
study drug. The dose a patient receives will depend on the number of participants who have
been enrolled in the study before that patient and how well they have tolerated their doses.

For this study, treatment will be broken up into segments. Study treatment will occur in two
segments: 1) Re-Induction Therapy; and 2) Maintenance Therapy. Re-induction therapy, as
described above, will be the combination of brentuximab vedotin followed on day 3 by MEC
chemotherapy. The maintenance phase of therapy will only include brentuximab vedotin
administered every 21 days for a total period of 12 months, and does not include any other
chemotherapy. The treatment and assessments that may be required fo patients during these
phases of therapy are explained below. The following assessments will be completed while
patients are on the trial: physical exam, performance status, urine test, blood tests and
bone marrow aspirate/biopsy.

The first part of the study treatment is called "re-induction". During re-induction, patients
will be admitted to the Massachusetts General Hospital and will receive study treatment on an
in-patient basis. Patients will receive brentuximab vedotin IV (intravenously or through a
vein) alone on Day 1. They will then receive the following standard drugs (the MEC regimen)
starting on day 3. This regimen includes the chemotherapy drugs mitoxantrone, etoposide, and
cytarabine, all given by IV and beginning on Day 3 and continuing through Day 7.

If at the end of the re-induction course, the number of leukemia cells have not decreased as
much as expected or desired, patients will be removed from the study and given alternative
options.

The second part of study treatment is called "maintenance" and can be given on an outpatient
basis in clinic. During maintenance, patients will be administered brentuximab vedotin once
every 21 days, at the same dose as that given during the re-induction course. This 21 day
period will be called a cycle, and will be repeated until 12 months have passed from the
start of the maintenance therapy phase. During this phase, participants will not receive
other chemotherapies and will not be hospitalized for treatment. During the maintenance
phase, investigators will continue to collect approximately 2 to 3 teaspoons of blood for
research purposes every 3-4 weeks.

Investigators would like to keep track of patients' medical condition and overall health
following the 12 months of treatment on study. Investigators may ask patients questions about
their general health, current medications and disease status. Investigators will also check
on any new anticancer therapy patients may have started.

Inclusion Criteria:

- Pathologically confirmed, relapsed acute myelogenous leukemia following a remission
duration of at least 3 months

- CD30 expressing AML

- Willing to use acceptable method of contraception

Exclusion Criteria:

- Have received systemic antineoplastic therapy, including radiotherapy within 14 days
of study treatment

- Pregnant or breastfeeding

- Diagnosis of acute promyelocytic leukemia

- Refractory acute myeloid leukemia

- History of a different malignancy except if disease free for at least 5 years and at
low risk of remission or one of the following within the past 5 years: cervical cancer
in situ, basal cell or squamous cell carcinoma of the skin

- Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy

- Uncontrolled intercurrent illness

- HIV positive on combination antiretroviral therapy

- Diagnosis of active hepatitis B or C

- Current or history of congestive heart failure NYHA class 3 or 4

- Current or history of ventricular or life-threatening arrythmias or diagnosis of
long-QT syndrome

- Systemic infection requiring IV antibiotic therapy within 7 days before first dose of
study drug