NCT00840853

Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT

Phase I Study of the Administration of Multi-Virus-Specific Cytotoxic T Lymphocytes Expressing CD19 Chimeric Receptors for Prophylaxis or Therapy of Relapse of CD19 Positive Malignancies Post Hematopoietic Stem Cell Transplantation

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

Subjects are having a bone marrow or SCT for either a type of cancer of the blood called Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant can cure leukemia or lymphoma, some people will relapse. In those who relapse, current treatment cures only a very small percentage. Although giving patients a dose of donor immune cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a serious complication called graft versus host disease (GVHD). This is a gene transfer research study using special immune cells which are specific for these cancer cells. The body has different ways of fighting infection and disease. This study combines 2 of those ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used to treat patients with cancers; they have shown promise, but haven't been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells because of a substance on the outside of these cells called CD19. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric receptor. In the laboratory, investigators found that T cells that are trained to recognize common viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to CTLs that recognize viruses, they believe that they will also be able to make a cell that can last a long time in the body, provide protection from viruses, and recognize and kill leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses (trivirus-specific CTLs), CMV, EBV, and adenovirus. Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given safely to transplant recipients and can stop these viruses from causing severe infections. These CD19 chimeric receptor trivirus specific T cells are an investigational product not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to assess the side effects, to see how long the T cells last and to evaluate whether this therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma having a SCT.

Detailed description

The donor gave us blood to make CD19 chimeric receptor trivirus specific T cells in the laboratory. These cells were grown and frozen for the subject. To make these special T cells they are grown with stimulator cells. Stimulator cells are also made from the donor's blood but they are irradiated so that they can no longer grow. Stimulator cells have been infected with viruses so that they carry proteins from 3 viruses (CMV, adenovirus, and EBV). These cells are cultured with the T cells so that they can learn to see and attack cells infected with CMV, EBV and adenovirus. To get the CD19 antibody to attach to the surface of the T cell, an antibody gene was inserted into the T cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps to find the T cells in the blood after injected. Once sufficient numbers of T cells are made, the investigators freeze the cells and test them to make sure they kill CD19+ tumors cells and cells infected with CMV, EBV and adenovirus. Once testing is completed the cells will be ready to give to the subject. When the subject enrolls on this study, they will be assigned a dose of CD19 chimeric receptor trivirus specific T cells. The subject will be given an injection of cells into the vein through an IV line at the assigned dose. The injection will take about 20 minutes. Investigators will monitor the subject in the clinic after the injection for up to 3 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or The Methodist Hospital. To learn more about the way the CD19 chimeric receptor trivirus specific T cells are working and how long they last in the body, extra blood will be drawn. The total blood drawn during this study will not exceed 300 tsp. For subjects receiving the CTLs for treatment of their disease: If the subject has stable disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging studies or by blood count after the T-cell infusion, the subject can receive up to six additional doses of the T cells if they wish. After each T-cell infusion, the subject will be monitored. Because the subject will have received cells with a new gene in them the subject will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

Conditions

• Acute Lymphoblastic Leukemia (ALL)
• Chronic Lymphocytic Leukemia (CLL)
• Non Hodgkin's Lymphoma

Interventions

Type	Name	Description
GENETIC	CD19CAR/virus specific T cells	CD19CAR/virus specific T cells will be thawed and given by intravenous injection from day +30 post transplant.
DRUG	Benadryl and Tylenol	Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.

Timeline

• Start date: 2009-04-01
• Primary completion: 2016-04-01
• Completion: 2031-04-01
• First posted: 2009-02-10
• Last updated: 2025-07-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study