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

Patients are being asked to participate in this study because they will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, they will be given very strong doses of chemotherapy, which will kill off all their existing stem cells. Stem cells are created in the bone marrow. They grow into different types of blood cells that we need, including red blood cells, white blood cells, and platelets. We have identified a close relative of the patients whose stem cells are not a perfect match for the patient, but can be used. This type of transplant is called "allogeneic", meaning that the cells come from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing graft-versus-host disease (GvHD) and a longer delay in the recovery of the immune system. GvHD is a serious and sometimes fatal side effect of stem cell transplant. GvHD occurs when the new donor cells recognize that the body tissues of the patient are different from those of the donor. In the laboratory, we have seen that cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. To get the iCasp9 into the T cells, we insert it using a virus called a retrovirus that has been made for this study. The drug (AP1903) that will be used to "activate" the iCasp9 is an experimental drug that has been tested in a study in normal donors, with no bad side effects. We hope we can use this drug to kill the T cells. Other drugs that kill or damage T cells have helped GvHD in many studies. However we do not yet know whether AP1903 will kill T cells in humans, even though it has worked in our experimental studies on human cells in animals. Nor do we know whether killing the T cells will help the GvHD. Because of this uncertainty, patients who develop significant GvHD will also receive standard therapy for this complication, in addition to the experimental drug. We hope that having this safety switch in the T cells will let us give higher doses of T cells that will make the immune system recover faster. These specially treated "suicide gene" T cells are an investigational product not approved by the Food and Drug Administration.

Sex

All

Maximum age

65 Years

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.

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