Kappa-CD28 T Lymphocytes, Chronic Lymphocytic Leukemia, B-cell Lymphoma or Multiple Myeloma, CHARKALL — CHARKALL  

Lymphoma Clinical Trial

Official title: Phase I Study of Adoptive Transfer of Autologous T Lymphocytes Engrafted With a Chimeric Antigen Receptor Targeting the Kappa Light Chain of Immunoglobulin Expressed in Patients With CLL, B-Cell Lymphoma or Multiple Myeloma

Status Recruiting

Clinical Trial Summary

Patients have a type of cancer called NHL, Multiple Myeloma (MM) or CLL that has come back or has not gone away after treatment. There is no standard treatment for the cancer at this time or the currently used treatments do not work completely in all cases like these. This is a gene transfer research study using special immune cells.

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, that investigators hope will work together. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients.

The antibody used in this study recognizes a protein on the lymphoma, MM or CLL cells called kappa immunoglobulin. Antibodies can stick to lymphoma, MM or CLL cells when it recognizes the kappa molecules present on the tumor cells. For this study, the kappa antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are limited.

In the laboratory, investigators found that T cells work better if they also add a protein that stimulates T cells to grow called CD28. By joining the anti-kappa antibody to the T cells and adding the CD28, the investigators expect to be able to make cells that will last for a longer time in the body (because of the presence of the CD28). They are hoping this will make the cells work better.

Previously, when patients enrolled on this study, they were assigned to one of three different doses of the kappa-CD28 T cells. We found that all three dose levels are safe. Now, the plan is to give patients the highest dose that we tested.

These chimeric T cells (kappa-CD28) are an investigational product not approved by the FDA.

Clinical Trial Description

To prepare the lymphoma, MM or CLL specific T cells investigators will take 240 ml (up to 16 tablespoonfuls)of blood from the patient. This would be drawn as 2 (two) separate blood collections of 120 ml (up to 8 tablespoonfuls) of blood.

To get the kappa antibody (with CD28) to attach to the surface of the T cell, investigators inserted the antibody gene 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 investigators find the T cells in the patient's blood after they're injected. Because the patient has received cells with a new gene in them patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

Several studies suggest that the infused T cells need room to be able to grow and accomplish their functions and that this may not happen if there are too many other T cells in circulation. Because of that, if the level of circulating T cells is relatively high or the patient has B-CLL, the patient may receive treatment with cyclophosphamide and fludarabine (Cy and Flu) prior to the infusion of the T cells. This drug will decrease the numbers of the patients own T cells before infusion of the kappa-CD28 T cells. Although investigators don't expect any effect on the tumor with the dose that the patient will receive, this drug is part of many regimens that are used to treat lymphoma, MM or CLL. If you are already receiving chemotherapy, this may not be needed.

Patients will be given an injection of cells into the vein through an IV line. If s/he receives Cy and Flu as stated above, the T cells will be given no sooner than 24 hours afterwards. If the patient has recently received other chemotherapy, the T cells will be given at least 24 hours after their last chemotherapy. The injection will take about 20 minutes. Investigators will follow the patient in the clinic after the injection. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

If after a 4-6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), the patient may be able to receive additional doses of the T cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the same dose level they received the first time or a lower dose. If the patient's circulating T cells are relatively high prior to any additional doses of T cells, they may receive Cy and Flu beforehand. ;

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Myeloma
• Neoplasms, Plasma Cell

• NCT number: NCT00881920
• Study type: Interventional
• Source: Baylor College of Medicine
• Contact: Carlos Ramos, MD
• Phone: 832-824-4817
• Email: caramos@txch.org
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2009
• Completion date: July 2035