CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene

Because the patient will receive cells with a new gene in them, they will be followed for a
total of 15 years to see if there are any long-term side effects of the gene transfer.

Before the conditioning treatment for the transplant, we collected 30 mL (6 teaspoonfuls) of
blood from the patient, which we made into a cell line that grows in the laboratory by mixing
the blood with a virus called EBV. Some of the cells from this blood were mixed with T cells
from the blood stem cell donor, to stimulate cells that might cause GvHD. We then added an
investigational agent called RFT5-dgA. The RFT5-dgA helped to get rid of donor T cells that
might cause GvHD. To get iCasp9 into the remaining T cells, we have to insert the iCasp9 gene
into these cells. This is done with a virus called a retrovirus that has been made for this
study, and will carry the iCasp9 gene into the T cells. The virus also has another gene
called CD19, which will make the cells express the CD19 protein on their surface. We will not
inject the virus directly into the patient, but only into the special T cells we have made in
the laboratory. After we have put the virus into the cells, we will select the T cells that
have CD19 on their surface, so we know these cells will also have the iCasp9 gene. We will
perform tests on the specially treated cells before giving them to the patient, to ensure
they only carry the iCasp9 gene, and not the virus itself. This should ensure that no virus
can come out of the cells and infect other cells in the body.

TREATMENT PLAN:

To prepare the body for transplantation, the patient will be given high-dose chemotherapy.
Further discussion of the treatment plan for the stem cell transplant will be discussed with
the patient separately, and they will sign a separate consent form.

If the patient is doing well after the transplant, and they do not have serious GvHD, they
will be eligible to receive the special T cells from Day 30 to 90 post-transplant. The
specially selected and treated T cells will be given by vein, once. The cells will be given
between Day 30 and day 90 after the patient receives their stem cell transplant. We will give
special medicines before the IV starts to help prevent allergic reactions that might occur.
Because there is a possibility that the specially treated T cells can cause or worsen GvHD,
we will not be able to give these cells if the patient already has significant GvHD.

If the patient develops GvHD after being given the specially treated T cells, we will
prescribe the new drug that has been shown to kill cells carrying iCasp9. The drug's name is
AP1903. It has been tested in normal healthy volunteers, and has not caused any bad effects,
but it is not approved by the FDA. Although the drug is not approved by the FDA, the FDA has
allowed us to use the drug for this study. This drug will be given as a 2-hour intravenous
infusion. We will take 10 mL (2 teaspoonfuls) of blood on days 2, 4, 7 and 14 after the
infusion to check if the drug has been successful in killing the specially treated cells. If
the patient has mild GvHD, and if the GvHD does not get better with AP1903, we will give the
patient additional medicines that are usually used to treat GvHD. If the patient has serious
GvHD, we will immediately give additional medicines that are usually used to treat GvHD, as
well as AP1903. In some cases though, GvHD does not respond to treatments.

INCLUSION CRITERIA:

At the time of transplant:

A. Patients (up to 65 years of age) with:

1. ALL or high grade NHL that is Stage III or IV and has relapsed or is considered to be
primary refractory disease.

2. Myelodysplastic syndrome.

3. AML after first relapse or with primary refractory disease.

4. CML

5. Hemophagocytic lymphohistiocytosis (HLH); familial hemophagocytic lymphohistiocytosis
(FLH); viral-associated hemophagocytic syndrome (VAHS); patients with severe chronic
active Epstein Barr virus infection (SCAEBV) with predilection for T or NK cell
malignancy; X-linked lymphoproliferative disease (XLP)

B. Lack of suitable conventional donor (i.e. 5/6 or 6/6 related, or 5/6 or 6/6 unrelated
donor) or presence of a rapidly progressive disease not permitting time to identify an
unrelated donor.

At the time of allodepleted T cell infusion:

1. Engrafted with ANC greater than 500.

2. Must have greater than or equal to 50% donor chimerism in either peripheral blood or
bone marrow, or relapse of their original disease.

3. Life expectancy greater than 30 days

4. Lansky/Karnofsky scores greater than or equal to 60

5. Absence of severe renal disease (creatinine greater than 2X normal for age)

6. Absence of severe hepatic disease (direct bilirubin greater than 2 mg/dL, or SGOT
greater than 200

7. Oxygen saturation greater than 94% on room air

8. Patient/Guardian able to give informed consent

EXCLUSION CRITERIA:

At the time of transplant:

1. Pregnancy*

At the time of allodepleted T cell infusion:

1. GvHD

2. Severe intercurrent infection

3. Pregnancy*

4. Other investigational drugs in the prior 30 days

- Pregnancy test only required for at-risk individuals, defined as female patients
of childbearing potential who have received a reduced-intensity conditioning
regimen.