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

Running, not enrolling · Phase 1

Conditions studied: Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Non Hodgkin Lymphoma, Hemophagocytic Lymphohistiocytosis, Familial Hemophagocytic Lymphohistiocytosis, Hemophagocytic Syndrome, Epstein Barr Virus Infection, X-linked Lymphoproliferative Disease

In brief

Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells. A close relative of the patient will be identified, whose stem cells are not a perfect match for the patient's, but can be used. This type of transplant is called "allogeneic", meaning that the cells are from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing 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 (graft) recognize that the body tissues of the patient (host) are different from those of the donor. In this study, investigators are trying to see whether they can make special T cells in the laboratory that can be given to the patient to help their immune system recover faster. As a safety measure, we want to "program" the T cells so that if, after they have been given to the patient, they start to cause GvHD, we can destroy them ("suicide gene"). Investigators will obtain T cells from a donor, culture them in the laboratory, and then introduce the "suicide gene" which makes the cells sensitive to a specific drug called AP1903. If the specially modified T cells begin to cause GvHD, the investigators can kill the cells by administering AP1903 to the patient. We have had encouraging results in a previous study regarding the effective elimination of T cells causing GvHD, while sparing a sufficient number of T cells to fight infection and potentially cancer. More specifically, T cells made to carry a gene called iCasp9 can be killed when they encounter the drug AP1903. To get the iCasp9 gene into T cells, we insert it using a virus called a retrovirus that has been made for this study. The 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. The major purpose of this study is to find a safe and effective dose of "iCasp9" T cells that can be given to patients who receive an allogeneic stem cell transplant. Another important purpose of this study is to find out whether these special T cells can help the patient's immune system recover faster after the transplant than they would have otherwise.

Key facts

Study ID: NCT01494103
Run by: Baylor College of Medicine
People needed: 15
Starts: 2011-11-01
Expected to finish: 2029-05-01
Last updated by the study team: 2026-07-01

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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.

Where it is running

Texas Children's Hospital — Houston, Texas, United States
The Methodist Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

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