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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary:

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. Seventy to ninety percent (70-90%) of people who receive unchanged marrow or stem cells from this type of donor will develop severe GvHD.

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. When this happens, cells in the graft may attack the host organs, primarily the skin, liver and intestines, causing severe rashes, diarrhea, liver disease, and even death. GvHD is caused by a type of immune cell in the graft called T cells. Because there is a high risk of GvHD with the type of transplant the patient will receive, we will selectively remove the T cells from the graft that the patient will receive. This process, which is called "CD34 selection", is discussed in more detail in the separate consent form for the transplant.

While this stem cell selection procedure will redu

Detailed Summary:

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 the gene transfer.

Before the conditioning treatment for the transplant, we collected 30 mL (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 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.

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Sponsor: Baylor College of Medicine

Current Primary Outcome:

  • To determine the maximum 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. [ Time Frame: 45 days ]
    Maximum tolerated dose of suicide gene-modified allodepleted donor lymphocytes up to a total of 1 x 10e7/kg per dose.
  • To evaluate the biological effects of administration of AP1903, a dimerizer used to activate the suicide gene mechanism, and its clinical effects in patients who develop GvHD. [ Time Frame: 1 year ]


Original Primary Outcome:

  • 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. [ Time Frame: 1 year ]
  • To evaluate the biological and clinical effects of administration of AP1903, a dimerizer used to activate the suicide gene mechanism, in patients who develop Grade 3 or 4 GVHD. [ Time Frame: 1 year ]


Current Secondary Outcome:

  • To analyze the contribution of the gene-modified cells to immune reconstitution in these patients by measuring their survival, persistence and expansion. [ Time Frame: 15 years ]
  • To measure the overall and disease-free survival at 100 days and at 1 year post-transplant. [ Time Frame: 1 year ]
  • To obtain preliminary information on whether subjects receiving additional doses of cells show a cumulative rise in the percentage of circulating gene-modified cells. [ Time Frame: 15 years ]


Original Secondary Outcome:

  • To analyze the contribution of the gene-modified cells to immune reconstitution in these patients by measuring their survival, persistence and expansion [ Time Frame: 15 years ]
  • To measure the overall and disease free survival, at 100 days and at 1 year [ Time Frame: 1 year ]


Information By: Baylor College of Medicine

Dates:
Date Received: July 3, 2008
Date Started: December 2008
Date Completion: July 2026
Last Updated: April 3, 2017
Last Verified: April 2017