Administration of Donor T Cells With the Caspase-9 Suicide Gene

If the patient is doing well after the stem cell transplant, and does not have severe GvHD, s/he will be eligible to receive the special "iCasp9" T cells from Day 30 to 90 after transplant. The specially selected and treated T cells will be given by vein (IV) once.

This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 5 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 5 dose levels are studied. If the side-effects are too severe, the dose will be lowered or the T cell injections will be stopped.

If the patient develops GvHD after being given the specially treated T cells, we will prescribe AP1903, which has been shown to kill cells carrying the iCasp9 gene. This drug will be given as a 2-hour IV infusion.

We will continue to follow the patient weekly in the bone marrow transplant clinic for the first month after the infusion, to check for side-effects of the treatment and for GvHD. The patient will have the standard tests performed that all patients have after transplant, even when not receiving special T cells.

Inclusion criteria

Inclusion criteria

at Time of Procurement:

• Lack of a 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.
• High risk disease in one of the following:

• Myelodysplastic syndrome (MDS) in one of the following categories: RCMD with an IPSS-R of intermediate, poor, or very poor, RAEB-1, or RAEB-2
• Acute myeloid leukemia (AML) after first relapse or primary refractory disease
• Chronic myelogenous leukemia (CML) in Chronic Phase 2 or greater, Accelerated Phase or Blast Crisis
• Acute lymphoblastic leukemia (ALL) after first relapse or primary refractory disease, or High-Grade Non Hodgkin lymphoma (NHL) Stage III or IV after first relapse or primary refractory disease
• Hemophagocytic lymphohistiocytosis (HLH)
• Familial hemophagocytic lymphohistiocytosis (FLH)
• Viral-associated hemophagocytic syndrome (VAHS)
• T or NK cell lymphoproliferative syndrome
• X-linked lymphoproliferative disease (XLP)

Inclusion criteria

at Time of T Cell Infusion:

• Engrafted with an absolute neutrophil count (ANC) > 500 cells/µL
• Greater than or equal to 50% donor chimerism in either peripheral blood or bone marrow, or relapse of their original disease
• Life expectancy > 30 days
• Lansky/Karnofsky score greater than or equal to 60
• Absence of severe renal disease (creatinine > 2X upper limit of normal for age)
• Absence of severe hepatic disease (direct bilirubin > 3X upper limit of normal or SGOT > 3X upper limit of normal)
• Oxygen saturation > 94% on room air
• Patient/Guardian able to give informed consent
• AP1903 available in sufficient quantities to allow for treatment of the patient

Exclusion criteria

Exclusion criteria

at Time of T Cell Infusion:

• GvHD
• Severe intercurrent infection
• Pregnancy*
• 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.