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

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.

Conditions

• Lymphoma
• Myeloma
• Leukemia

Interventions

BIOLOGICAL

Kappa CD28 T cells

T cells will be given in a lymphopenic environment utilizing (as needed) lymphodepleting chemotherapy (Cy/Flu) prior to T cell infusion as outlined below: Patients who are not lymphopenic may receive 3 daily doses of cyclophosphamide (500mg/m2/day) together with fludarabine (30mg/m2) to induce lymphopenia, finishing at least 24 hours before T cell infusion. Patients with lymphopenia due to current drug therapy may be infused at any time starting at least 24 hours after finishing their current cycle of chemotherapy. ASCT recipients (relapsed/refractory intermediate grade lymphoma) may be infused 14-60 days after the date of transplant. T cell dosing is as follows: Group 1: 2x10\^7 cells/m\^2 CAR-Kappa Group 2: 1x10\^8 cells/m\^2 CAR-Kappa Group 3: 2x10\^8 cells/m\^2 CAR-Kappa

Sponsors & Collaborators

• The Methodist Hospital Research Institute

  collaborator OTHER

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Carlos Ramos, MD · Baylor College of Medicine - Texas Children's Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-07-31

Primary Completion

2018-07-31

Completion

2035-07-31

FDA Drug

Yes

Countries

• United States

Study Locations