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

Phase 1
Open (Enrolling)
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

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Trial Information

Administration of Haploidentical Donor T Cells Transduced With the Inducible 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 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 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 :

1. 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

2. 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:

1. Engrafted with an absolute neutrophils count (ANC) >500 cells/┬ÁL.

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

3. Life expectancy >30 days

4. Lansky/Karnofsky score 60 or greater

5. Absence of severe renal disease (Creatinine >2X upper limit of normal for age)

6. Absence of severe hepatic disease (direct bilirubin >3X upper limit of normal or SGOT
>3X upper limit of normal)

7. O2 sat >94% on room air

8. Patient/Guardian able to give informed consent.

9. AP1903 available in the Investigational Pharmacy (required 0.4mg/Kg per dose; vial
concentration 5mg/mL, total volume per vial=2 mL).

Exclusion Criteria:

Exclusion Criteria at time of T cell infusion:


2. Severe intercurrent infection

3. Pregnant*

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 has received a reduced intensity conditioning

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical and Immunological effects of AP1903 administration

Outcome Description:

To evaluate the clinical and immunological effects of AP1903 administration, a dimerizer drug used to activate an iCaspase9 suicide gene mechanism, to subjects who have received escalating doses of T lymphocytes expressing the iCaspase9 gene and developed acute graft-versus-host-disease (GvHD).

Outcome Time Frame:

15 years

Safety Issue:


Principal Investigator

Malcolm K Brenner, MB, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

July 2030

Related Keywords:

  • 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
  • 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
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphohistiocytosis, Hemophagocytic
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Myelodysplastic Syndromes
  • Preleukemia
  • Suicide
  • Virus Diseases
  • Epstein-Barr Virus Infections



Texas Children's Hospital Houston, Texas  
The Methodist Hospital Houston, Texas  77030