CAR T Cell Receptor Immunotherapy for Patients With B-cell Lymphoma

Summary

Background:

The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with B cell lymphomas or leukemias that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-cluster of differentiation 19 (CD19) incorporated in the retrovirus.

Objective:

The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-CD19 cells) cause tumors to shrink.

Eligibility:

\- Adults age 18-70 with B cell lymphomas or leukemias expressing the CD19 molecule.

Design:

Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed

Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-CD19 cells. Leukapheresis is a common procedure, which removes only the white blood cells from the patient.

Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy and the anti-CD19 cells. They will stay in the hospital for about 4 weeks for the treatment.

Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Conditions

• Primary Mediastinal B-cell Lymphoma
• Diffuse, Large B-cell Lymphoma
• Diffuse Large B-Cell Lymphoma Transformed From Follicular Lymphoma
• Mantle Cell

Interventions

DRUG

Fludarabine

Days -5 to -1 (after administration of cyclophosphamide): 25 mg/m\^2 intravenous (IV) over 30 minutes

DRUG

Cyclophosphamide

Days -5 to -4: 60mg/kg intravenous (IV) over 60 minutes

BIOLOGICAL

Anti-cluster of differentiation 19 (CD19)-CAR PBL

Anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) peripheral blood lymphocytes ( PBL). Day 0 (two to four days after the last dose of fludarabine); Cells will be infused via intravenous (IV) on the Patient Care Unit over 20-30 minutes.

DRUG

Aldesleukin

Day 0: 720,000 IU/kg intravenously (IV) every 8 hours for a maximum of 15 doses.

DRUG

Fludarabine

Days -5 to -3 (after administration of cyclophosphamide): 30 mg/m\^2 intravenous (IV) over 30 minutes

DRUG

Cyclophosphamide

Days -5 to -3: 300mg/m\^2 intravenous (IV) over 60 minutes

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven A Rosenberg, M.D., Ph.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-02-17

Primary Completion

2015-09-30

Completion

2021-11-17

FDA Drug

Yes

Countries

• United States

Study Locations