Her2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma

Summary

Patients have a type of cancer called sarcoma. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing or exerting their toxic effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients. We have found from previous research that we can put a new gene into T cells that will make them recognize cancer cells and kill them. We now want to see if we can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that we will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition it contains CD28, which stimulated T cells and make them last longer. In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of patient's lymphocytes first should allow the T cells we infuse to expand and stay longer in your body, and potentially kill cancer cells more effectively. We will use fludarabine or the combination of cyclophosphamide and fludarabine as the chemotherapy agents for lymphodepletion. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials. The purpose of this study is to find the largest safe dose of chimeric T cells, and to see whether this therapy might help patients with sarcoma. Another purpose is to see if it is safe to give HER2-CD28 T cells after lymphodepleting chemotherapy.

Conditions

• Sarcoma

Interventions

GENETIC

Autologous HER2-specific T cells

Each patient will receive one intravenous injection of autologous HER2-specific T cells at one of the dose levels. If the patient has stable disease or a reduction in the size of the tumor they can receive additional doses of HER2-specific T cells at 6 to 12 weeks intervals-each of which will consist of the same cell number as their HER2-specific T-cell injection. For the first two subsequent HER2-specific T-cell infusions, patients will be able to receive additional lymphodepleting chemotherapy according to their dose levels.

DRUG

Fludarabine

Fludarabine will be administered for 5 days prior to the T cells The dose: \>10 kg: 25 mg/m2/day; \<10 kg: 1 mg/kg/day IV over 30 minutes

DRUG

Cyclophosphamide

Cyclophosphamide will be administered for 2 days. Fludarabine and cyclophosphamide will be given for 2 days, followed by fludarabine alone for the next 3 days, followed by 2 days of rest, before the T cells will be administered. Cyclophosphamide Dose: 30 mg/kg/day IV over 1 hour (with Mesna and IV hydration) Fludarabine Dose: \>10 kg: 25 mg/m2/day; \<10 kg: 1 mg/kg/day IV over 30 minutes

GENETIC

Autologous CAR Positive T cells

Patient will receive one intravenous injection of autologous CAR T cells at dose level 9C. Further CAR T-cell dose escalation at dose level 9C will be done using the lymphodepletion schema as in dose level 9B.

Sponsors & Collaborators

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

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• Cancer Prevention Research Institute of Texas

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Nabil M Ahmed, MD · Baylor College of Medicine - Texas Children's Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-02-11

Primary Completion

2019-12-06

Completion

2032-07-31

Countries

• United States

Study Locations