Using Gene Modified Neuroblastoma Cells for the Treatment of Relapsed/Refractory Neuroblastoma

NCT ID: NCT00062855

Last Updated: 2012-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-11-30

Study Completion Date

2006-03-31

Brief Summary

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This research study is designed to determine the safety and dosage of special cells that may make a patients own immune system fight the cancer. To do this we will put two special genes into cancer cells taken from the patients body. The genes we put in make the cancer cells produce lymphotactin, a natural substance that attracts immune system cells to the cancer, and IL-2 a natural substance that may help the immune system kill cancer cells. Some of these cells will then be put back in the patient's body. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that substances like lymphotactin and IL-2 help the body kill cancer cells. A treatment similar to this has been used in ten children previously and similar treatments are being used in adults with other cancers.

The purpose of this study is to learn the side effects and safe 'dosage' of these special cells.

Detailed Description

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Neuroblastoma cells taken from the patient will be separated in the laboratory and two specially produced human viruses (adenovirus) that carry the lymphotactin and the IL-2 gene were put into the cells. These lymphotactin and IL-2 genes are meant to help the immune system fight the cancer.

The modified cancer cells will be injected under the patient's skin. There will be four shots. The second and subsequent shots will have ten times as many cells producing lymphotactin as the first. We do not know the best amount of special cells to use, so different patients will get different numbers of cells.

Before the second shot, and then again about 2 weeks later, we will remove some of the modified cells from the patient's body and study them. We will do this by removing a section of skin (referred to as a skin biopsy) at the place where the cells were injected. This test will help us to see whether or not the modified cells are killing cancer cells.

To study how the immunity is working in the patient's system, we will take blood samples prior to each injection, two to four days after each injection, and may repeat this 5-7 days after each injection if your doctor thinks that is necessary.

After patients have received the first set of 4 injections a complete evaluation is performed to see how this research treatment is working. If these evaluations look okay and if more injections are available, patients will have the option to receive a second set of 4 injections. If patients receive the second set of 4 injections, they will again have blood samples taken after each injection.

After injections stop, all patients will have blood samples collected once a month for a year, and then once a year for fifteen years.

To see if this research treatment is working, we will do CAT scans, MRIs, or bone scans (these are different types of x-rays). We will also take a bone marrow biopsy (bone marrow will be removed by use of a needle so that it can be looked at under the microscope). These tests will be done prior to treatment and again eight weeks later. In addition, if patients receive the second set of four injections, these tests will be repeated at six months.

Conditions

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Neuroblastoma

Keywords

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GENE MODIFIED AUTOLOGOUS NEUROBLASTOMA CELLS Gene Therapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gene Modified Neuroblastoma Cells

Gene modified neuroblastoma cells given as 4 subcutaneous injections over 5 weeks

Group Type EXPERIMENTAL

Skin Biopsy

Intervention Type PROCEDURE

Gene Modified Neuroblastoma Cells

Intervention Type GENETIC

The first two injections will be given at week 1 and week 2 (i.e., separated by one week). Patients will then have a two-week rest and the remaining two injections will be given (again separated by one week) at week 4 and week 5.

A complete evaluation for evidence of toxicity and response will be performed at week 8 (after a 3 week rest).

At the 8 week (month 2) evaluation, in the absence of progressive disease requiring therapy without excessive toxicity and if more transduced cells are available, the patient will have the option to receive four additional SC injections each separated by 1 month at the higher of the two dosage levels they originally received.

Interventions

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Skin Biopsy

Intervention Type PROCEDURE

Gene Modified Neuroblastoma Cells

The first two injections will be given at week 1 and week 2 (i.e., separated by one week). Patients will then have a two-week rest and the remaining two injections will be given (again separated by one week) at week 4 and week 5.

A complete evaluation for evidence of toxicity and response will be performed at week 8 (after a 3 week rest).

At the 8 week (month 2) evaluation, in the absence of progressive disease requiring therapy without excessive toxicity and if more transduced cells are available, the patient will have the option to receive four additional SC injections each separated by 1 month at the higher of the two dosage levels they originally received.

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* All patients under 21 years of age at diagnosis with recurrent, advanced stage neuroblastoma.
* Patients must have a life expectancy of at least 8 weeks.
* Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute lymphocyte and neutrophil count of \>500/mm3 each.
* Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks.
* Patients must not be HIV-positive.
* Patients must have bilirubin \<1.5 mg%.
* Patients must have creatinine \<1.5 mg/dl.
* Patients must have ECOG performance status of 0-2.
* Patients must have autologous transduced neuroblastoma cells available that are demonstrably producing \>150 pg IL-2/106 cells/24 hr and are secreting Lptn.
* Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
* Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Center for Cell and Gene Therapy, Baylor College of Medicine

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Malcolm Brenner

Professor, Director Center for Cell and Gene Therapy

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Malcolm Brenner, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

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Texas Children's Hospital

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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Cyche

Identifier Type: -

Identifier Source: secondary_id

H6442

Identifier Type: -

Identifier Source: org_study_id

NCT00002713

Identifier Type: -

Identifier Source: nct_alias