Administration of Anti-CD19-chimeric-antigen-receptor-transduced T Cells From the Original Transplant Donor to Patients With Recurrent or Persistent B-cell Malignancies After Allogeneic Stem Cell Transplantation

Summary

Background:

* Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure that transplants bone marrow cells (stem cells) from a matching donor into a recipient in order to allow the donor stem cells to produce cells that will attack the recipient s cancer cells. AlloHSCT is performed when chemotherapy, immunotherapy, or radiation therapy do not adequately control cancer growth. However, cancers that are not controlled by alloHSCT frequently become resistant to other standard treatment options.
* The outcomes of alloHSCT might be improved if certain kinds of white blood cells (T cells) could be manipulated so that they generate a more potent effect against the cancer cells. This effect can be augmented by genetically engineering donor T cells to specifically recognize cancerous cells in order to attack them. For this purpose, researchers are studying a specific kind of genetically engineered T cell known as the anti-CD19-CAR-transduced T cell. More research is needed to determine if this T cell will be an effective treatment for certain kinds of B cell cancer (such as non-Hodgkin s lymphoma and chronic lymphocytic leukemia) that has not been controlled with alloHSCT.

Objectives:

\- To assess the safety and effectiveness of administering allogeneic anti-CD19-CAR-transduced T cells to patients with B-cell cancer that has not responded to alloHSCT.

Eligibility:

* Individuals between 18 and 75 years of age who have received allogeneic hematopoietic stem cell transplantation for a B cell cancer, but whose cancer has either not responded to or recurred after the transplant.
* Recipients must have the same stem cell donor from their previous procedure.

Design:

* Before the start of the study, all participants will be screened with a medical history and blood tests. Recipients will have tumor imaging scans, additional blood tests, and other tests as directed by the study doctors.
* Donor participants will undergo apheresis to provide white blood cells for researchers to use in the treatment.
* Recipients will have dose escalation to determine the most effective yet safe dose of anti-CD19 T cells. There will be six dose levels of anti-CD19 T cells. The first patients enrolled will have the smallest dose, and the dose will be increased when a level has been determined to be safe. .
* Recipients will be hospitalized for at least 9 days after receiving the cell infusion, and will need to come to clinic for follow-up visits 2, 4, 8, and 12 weeks after the infusion.
* Additional scans and frequent blood tests will be required for the first 3 months after the infusion, followed by less frequent visits over time.
* Recipients will be followed for a maximum of 15 years after receiving the infusion.

Conditions

• Leukemia, B-cell
• Lymphoma, Hodgkins
• Lymphoma, Non-hodgkins
• Lymphoma, B-Cell

Interventions

PROCEDURE

Allogeneic stem cell transplant

Allogeneic stem cell transplant

BIOLOGICAL

Anti-CD19-chimeric-antigen-receptor-transduced T cells

Patients receive T cells genetically engineered to express an anti-CD19 CAR. The cells are cultured in media containing IL-21, IL-7, and TWS119. TWS119 is a glycogen synthase 3 inhibitor

PROCEDURE

Leukapheresis

Donors will undergo leukapheresis

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• James N Kochenderfer, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-08-04

Primary Completion

2024-03-08

Completion

2024-04-02

FDA Drug

Yes

Countries

• United States

Study Locations