Gene Modified Allogeneic Neuroblastoma Cells For Treatment of Relapsed/Refractory Neuroblastoma - Full Text View

Sponsors and Collaborators:	St. Jude Children's Research Hospital Texas Children's Cancer Center National Cancer Institute (NCI)
Information provided by:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00186862

Purpose

Neuroblastoma affects approximately 500 children a year in the United States. When the tumor occurs in infants, it is frequently localized and responds well to therapy. Even disseminated disease can be eradicated in about 75% of infants, and indeed may undergo spontaneous remission. In older children, the prognosis is far worse, and 80% or more of those with disseminated tumor can be expected to relapse within 3 years.

This study will utilize the concept of exploiting the immune system to eradicate neuroblastoma. In tumors in which there is consistent expression of tumor specific antigens as part of the malignant process, it may be possible to generate immune T-cells ex-vivo or in-vivo by using the specific protein or peptide(s) derived therefrom and eradicate the tumor. This study will evaluate the use of four to eight injections of IL-2 gene-transduced autologous neuroblastoma cells to induce a local, polyclonal T-cell infiltrate as well as an anti-tumor immune response.

Condition	Intervention	Phase
Neuroblastoma	Drug: Interleukin-2	Phase I

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Interleukin-2

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase I Study of Chemokine and Cytokine Gene Modified Allogeneic Neuroblastoma Cells For Treatment of Relapsed/Refractory Neuroblastoma Using a Retroviral Vector

Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:

• To determine the safety of up to eight subcutaneous injections of allogeneic neuroblastoma cells that have been genetically modified by retroviral vectors to secrete lymphotactin and Interleukin-2 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment:	24
Study Start Date:	August 1998
Study Completion Date:	October 2007
Primary Completion Date:	April 2000 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1	Drug: Interleukin-2 A genetically modified (retroviral) allogeneic tumor vaccine coupled with the human interleukin-2. Patients were treated with 4 injections of these gene-modified tumor cells. The first two were given at weeks 1 and 2. Patients then had a 2 week rest and the remaining 2 injections were given at weeks 4 and 5. A complete evaluation for evidence of toxicity and response were performed at week 8. At this week 8 evaluation, if there was no excessive toxicity, progressive disease requiring therapy, and if more transduced cells are available, patients had the option to receive 4 additional injections. These additional injections were separated by 1 month at the higher of the two dosage levels originally received.

Arms

Assigned Interventions

1

Drug: Interleukin-2

A genetically modified (retroviral) allogeneic tumor vaccine coupled with the human interleukin-2. Patients were treated with 4 injections of these gene-modified tumor cells. The first two were given at weeks 1 and 2. Patients then had a 2 week rest and the remaining 2 injections were given at weeks 4 and 5. A complete evaluation for evidence of toxicity and response were performed at week 8.

At this week 8 evaluation, if there was no excessive toxicity, progressive disease requiring therapy, and if more transduced cells are available, patients had the option to receive 4 additional injections. These additional injections were separated by 1 month at the higher of the two dosage levels originally received.

Detailed Description:

Secondary objectives for this protocol included the following:

To determine whether major histocompatibility complex (MHC) restricted or unrestricted antitumor immune responses are induced by injection of modified allogeneic neuroblasts and the cell doses required to produce these effects.
To obtain preliminary data on the antitumor effects of this treatment regimen.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Diagnosis of recurrent advanced stage neuroblastoma.
Must have a life expectancy of at least 8 weeks.
Must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute neutrophil count of >500/mm3.
Not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six months.
Bilirubin <1.5 mg/dl.
Creatinine <1.5 mg/dl.
ECOG performance status of 0-2 as below:
Does not have rapidly progressive disease.
Not pregnant or lactating.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00186862

Locations

United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

St. Jude Children's Research Hospital

Texas Children's Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Gregory A Hale, MD

St. Jude Children's Research Hospital

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	St. Jude Children's Research Hospital ( Gregory Hale, MD )
Study ID Numbers:	CYCHAL
Study First Received:	September 12, 2005
Last Updated:	June 2, 2008
ClinicalTrials.gov Identifier:	NCT00186862 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:

Neuroblastoma
Immunotherapy
Gene therapy

Study placed in the following topic categories:

Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Analgesics, Non-Narcotic
Interleukin-2
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Peripheral Nervous System Agents
Analgesics
Neuroectodermal Tumors, Primitive, Peripheral
Neuroblastoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Pharmacologic Actions
Neuroblastoma
Neuroectodermal Tumors
Neoplasms
Sensory System Agents

Analgesics, Non-Narcotic
Interleukin-2
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Peripheral Nervous System Agents
Analgesics
Neoplasms, Neuroepithelial
Central Nervous System Agents
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009