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

This study has been completed.
Sponsor:
Collaborators:
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Malcolm Brenner, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00062855
First received: June 17, 2003
Last updated: October 26, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Procedure: Skin Biopsy
Genetic: Gene Modified Neuroblastoma Cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Chemokine and Cytokine Gene Modified Autologous Neuroblastoma Cells for Treatment of Relapsed/Refractory Neuroblastoma Using an Adenoviral Vector (CYCHE)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • To determine the safety of up to four subcutaneous (SC) injections of autologous neuroblastoma cells which have been genetically modified by adenoviral vectors to secrete lymphotactin (Lptn) and Interleukin-2 (IL-2). [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • To determine the safety of up to eight (total) of these injections in patients who have received the first four injections without unacceptable toxicity and have evidence of stable disease or better after receiving these injections. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine whether MHC restricted or unrestricted antitumor immune responses are induced by SC injection of modified autologous neuroblasts and the cell doses required to produce these effects. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • To obtain preliminary data on the antitumor effects of this treatment regimen [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: November 1997
Study Completion Date: March 2006
Primary Completion Date: August 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gene Modified Neuroblastoma Cells
Gene modified neuroblastoma cells given as 4 subcutaneous injections over 5 weeks
Procedure: Skin Biopsy Genetic: 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.


Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00062855

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Malcolm Brenner, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Malcolm Brenner, Professor, Director Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00062855     History of Changes
Obsolete Identifiers: NCT00002713
Other Study ID Numbers: H6442, Cyche
Study First Received: June 17, 2003
Last Updated: October 26, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
GENE MODIFIED AUTOLOGOUS NEUROBLASTOMA CELLS
Gene Therapy

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on October 01, 2014