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CASPALLO: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell Transplantation


Phase 1
N/A
65 Years
Open (Enrolling)
Both
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

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Trial Information

CASPALLO: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell Transplantation


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 gene transfer.

Before the conditioning treatment for the transplant, we collected 30ml (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 put the cells over a
column to 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 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 10mls (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
you have 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 give additional medicines that are usually used to treat GvHD as well as AP1903
immediately. In some cases though GvHD does not respond to treatments.

Inclusion Criteria


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.

Inclusion Criteria at 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 60 or greater

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

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

7. O2 sat greater than 94% on room air

8. Patient/Guardian able to give informed consent.

EXCLUSION CRITERIA:

At the time of transplant:

1. Pregnant*

At the time of allodepleted T cell infusion:

1. GVHD

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
regimen.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

To determine the number of suicide gene-modified allodepleted donor lymphocytes that can be given to recipients of haploidentical stem cell transplants that will result in a rate of Grade III/IV GVHD of 25% or less.

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Malcolm K Brenner, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

21580-CASPALLO

NCT ID:

NCT00710892

Start Date:

December 2008

Completion Date:

August 2028

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin's Lymphoma
  • suicide gene-modified allodepleted donor lymphocytes
  • given to recipients of haploidentical stem cell transplants
  • Stage III
  • Stage IV
  • Myelodysplastic syndrome
  • AML after first relapse
  • primary refractory disease
  • CML
  • Hemophagocytic lymphohistiocytosis (HLH)
  • familial hemophagocytic lymphohistiocytosis (FLH)
  • viral-associated hemophagocytic syndrome (VAHS)
  • Severe chronic active Epstein Barr virus infection (SCAEBV)
  • T or NK cell malignancy
  • X-linked lymphoproliferative disease (XLP)
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphohistiocytosis, Hemophagocytic
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Suicide

Name

Location

Texas Children's HospitalHouston, Texas  
The Methodist HospitalHouston, Texas  77030