T Cell Receptor Immunotherapy Targeting MAGE-A3 for Patients With Metastatic Cancer Who Are HLA-A*01 Positive

Summary

Background:

The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with cancer 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 patients white blood cells with a retrovirus that has the gene for anti-MAGE-A3 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-MAGE A3 cells) cause tumors to shrink and to be certain the treatment is safe

Eligibility:

\- Adults age 18-66 with cancer expressing the MAGE-A3 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 MAGE-A3 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, the anti MAGE-A3 cells and aldesleukin. 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 take up to 2 days.

Conditions

• Breast Cancer
• Cervical Cancer
• Renal Cancer
• Melanoma
• Bladder Cancer

Interventions

DRUG

Aldesleukin

Aldeskeukin 720,000 IU/kg (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).

DRUG

Fludarabine

Days -7 to -3: Fludarabine 25 mg/m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.

DRUG

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

BIOLOGICAL

Anti-MAGE-A3 human leukocyte antigen serotype within HLA-A A serotype group (HLA-A* 01)-restricted T-cell receptor (TCR)

Day 0: MAGE-A3-A1 transduced peripheral blood lymphocytes (PBL) will be infused intravenously on the Patient Care Unit over 20-30 minutes.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven A Rosenberg, M.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

2014-07-03

Primary Completion

2018-09-10

Completion

2018-09-10

FDA Drug

Yes

Countries

• United States

Study Locations