Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis

Study Treatment:

If you are found to be eligible to take part in this study, your doctor will assign you to
either Group 1 or Group 2.

You will receive the study treatment in 2 parts. The first part of the study will last about
8 weeks (Weeks 1-8) and will be called the "induction phase". The second part of the study
will start after the induction phase and will last about 16 weeks (Weeks 9-16). This part
will be called the "maintenance phase". However, the parts of the study may be longer or
shorter depending on if/how the disease responds to the treatment, how the biomarkers react
to treatment, and what the doctor thinks is in your best interest.

- If you are in Group 1, you will receive alemtuzumab by vein over 2 hours or through an
injection under the skin every day on Days 1-4 of the induction phase and about 1 time
every 4 weeks during the maintenance phase.

- If you are in Group 2, you will receive tocilizumab by vein over 60 minutes on Day 1 or
Day 2 of the Induction phase. Tocilizumab will not be given in the Maintenance Phase.

Participants in both Groups 1 and 2 will receive etoposide by vein about 1 time each week
during the induction phase. You will not receive it in the maintenance phase unless the
disease stops responding to the study drugs. At that point, you may begin to receive
etoposide again. The study doctor will tell you more about this.

The length of time it takes to infuse the study drugs will be different from patient to
patient and will depend on rate of injection. Your doctor will discuss this with you.

Participants in both Groups 1 and 2 will receive dexamethasone by vein on Days 1-7 of the
induction phase. After this, you will take pills of dexamethasone every day during the
induction phase. In the maintenance phase, you will take these pills 3 times each week with
at least a day between each dose (for example, Monday, Wednesday, and Friday).

Your dose of the study drugs may be raised, lowered, and/or delayed if the doctor thinks it
is in your best interest.

If the disease involves the central nervous system during the Induction phase, you may
receive methotrexate. Methotrexate is given 1 time a week for 5 weeks.

Study Visits:

You will have physical exams on the following days:

- Day 1,

- Every week for the first 4 weeks,

- Every 2 weeks during the next 4 weeks,

- Every 4 weeks during the next 16 weeks, and

- Every 8 weeks after that.

Blood (about 3 tablespoons) will be drawn for routine tests on the following days. During the
first 4 weeks, these tests must be performed at MD Anderson. After that, these can be
performed at a local clinic:

- Day 1,

- Two (2) times each week for the first 4 weeks,

- Every week for the next 4 weeks,

- Every 2 weeks for the next 16 weeks, and

- Every 4 weeks after that.

You will have a bone marrow aspiration/biopsy 4 weeks after starting the study treatment and
then every 4-12 weeks after that.

At any time that the doctor thinks it is needed, you may have additional blood draws or bone
marrow aspirations/biopsies to check the status of the disease. If you receive treatment for
longer than 24 weeks, the timing of these procedures may be changed if the study doctor
thinks it is in your best interest.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug 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 follow-up visits.

End-of-Study Visit:

If you are taken off or if you leave the study before you have received treatment for 24
weeks, the following tests and procedures will be performed within 30 days (+/- 7 days) of
the last dose of the study drug:

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

- If the doctor thinks it is needed, you will have a bone marrow aspirate to check the
status of the disease.

If you cannot make it to MD Anderson for this visit, these procedures may be done with a
local doctor and the records can be forwarded to the study doctor.

Follow-Up:

If you respond to the study drugs, you will be followed every 3-6 months for up to 5 years
after completion of treatment. You will be called and asked about how you are doing. Each
call will last about 5-10 minutes.

Inclusion Criteria:

1. Sign an IRB-approved informed consent document.

2. Patients must be >/= 18 years of age.

3. • A documentation of diagnosis of hemophagocytic lymphocytosis, either newly diagnosed
or relapsed/refractory by the treating physician and the PI in the patients chart. It
must be noted that no diagnostic criteria have been established for diagnosis of HLH
in adult patients as this was a hitherto poorly identified and considered to be a very
rare disease in adults. We have seen an increasing number of cases of HLH at our
institution over the last 2 years partly due to referrals and partly due to better
understanding of the disease through discussions with our collaborators Dr Kenneth
McClain and Dr Carl Allen at TCH (experts in pediatric HLH). Adult HLH seems to occur
more frequently post malignancy and has a more fulminant course than pediatric HLH.

4. Continued from No. 3: The diagnostic criteria that have been traditionally used for
children (HLH 1991 and HLH 2004) may not adequately diagnose HLH in adults. This is
the first adult HLH protocol in the country. In the absence of standard diagnostic
guidelines if the patient's symptoms are highly suspicious for HLH and after an
adequate work-up to rule out alternate potential alternate etiologies is performed we
will treat the patient for HLH as missing the diagnosis is associated with high
mortality. These patients will be discussed with the PI (Dr Daver) prior to enrollment
in all such cases.

5. Organ function as defined below (unless due to the HLH process): Serum creatinine 3.0 mg/dL, Total bilirubin related to the HLH process this must be clearly documented in the chart and the
patients may be enrolled on study irrespective of creatinine and bilirubin levels.

6. Women of childbearing potential must practice contraception. Females of childbearing
potential: Recommendation is for 2 effective contraceptive methods during the study.
Adequate forms of contraception are double barrier methods (condoms with spermicidal
jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or
injectable contraceptives, intrauterine devices, and tubal ligation. Male patients
with female partners who are of childbearing potential: Recommendation is for male and
partner to use at least 2 effective contraceptive methods, as described above, prior
to study entry and for at least 3 months after the last dose of study drug.

7. Negative urine pregnancy test and/or serum pregnancy test within 7 days of initiation
of therapy.

8. Male patients with female partners who are of childbearing potential: Recommendation
is for male and partner to use at least 2 effective contraceptive methods, as
described above, prior to study entry and for at least 3 months after the last dose of
study drug.

Exclusion Criteria:

1. Pregnant and breast feeding women

2. Any serious/and or unstable pre-existing medical disorder (aside from malignancy
exception above), psychiatric disorder, or other conditions that could interfere with
subject's safety, obtaining informed consent or compliance to the study procedures

3. Patients unwilling or unable to comply with the protocol.