T Lymphocytes and Anti-CD45 Monoclonal Antibody in Treating Patients With Advanced Neuroblastoma - Full Text View

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00609206

Purpose

RATIONALE: Gene-modified T lymphocytes may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as anti-CD45 monoclonal antibody, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving T lymphocytes together with anti-CD45 monoclonal antibody may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of T lymphocytes when given together with anti-CD45 monoclonal antibody in treating patients with advanced neuroblastoma.

Condition	Intervention	Phase
Neuroblastoma	Biological: anti-CD45 monoclonal antibody Biological: autologous Epstein-Barr virus-specific cytotoxic T lymphocytes Biological: therapeutic autologous lymphocytes Genetic: gene expression analysis Genetic: polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis	Phase I

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	ADMINISTRATION OF PERIPHERAL BLOOD T-CELLS AND EBV SPECIFIC CTLS TRANSDUCED TO EXPRESS GD-2 SPECIFIC CHIMERIC T CELL RECEPTORS TO PATIENTS WITH NEUROBLASTOMA

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Differential survival and function [ Designated as safety issue: No ]
Antitumor effects [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	July 2003
Estimated Primary Completion Date:	December 2021 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To evaluate the safety of escalating doses of 14g2a.zeta chimeric receptor transduced autologous Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (EBV-CTLs) and 14g2a.zeta transduced autologous peripheral blood T cells administered to patients with neuroblastoma who have been lympho-depleted by CD45 monoclonal antibodies.

Secondary

To determine the differential survival and function of these two infused cell-types in vivo, in particular to determine if chimeric receptor transduced EBV-CTLs survive longer than transduced peripheral-blood T cells.
To determine antitumor effects of transduced peripheral blood T cells and EBV-specific CTLs in vivo.

OUTLINE: This is a dose-escalation study of 14g2a.zeta transduced autologous Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) and 14g2a.zeta transduced autologous peripheral blood T cells

Patients receive anti-CD45 monoclonal antibody IV over 6-8 hours on days 1-4, and autologous EBV-CTL IV over 5-10 minutes and autologous peripheral blood T cells IV over 5-10 minutes on days 6-8.

Blood samples are collected periodically and analyzed for plasma free CD45 antibody levels by flow cytometry; phenotyping; EBV and transgene samples by PCR; and immune function and persistence studies, including oligo1 and oligo2 by quantitative real-time PCR, RCR testing by PCR, EBV viral load by quantitative real time PCR, interferon-γ release by ELISPOT, EBV-specific cytotoxic T lymphocytes by tetramer analysis, retroviral integrant clonality and integrant locus by LAM-PCR, expression of 14g2a.zeta by flow cytometry, and HAMA/HARA studies.

After completion of study therapy, patients are followed at 1, 2, 4, and 6 weeks, and every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years.

Eligibility

Ages Eligible for Study:	3 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Confirmed diagnosis of recurrent or refractory advanced-stage neuroblastoma, or newly diagnosed patients unable to receive or complete standard therapy
- Must be Epstein-Barr virus (EBV) sero-positive
Patients who received prior therapy with murine antibodies must have documentation of absence of human anti-mouse antibodies
Must have autologous transduced EBV-specific cytotoxic T lymphocytes and transduced peripheral blood T cells with ≥ 15% expression of 14g2a.zeta as determined by flow cytometry
Pulmonary metastatic lesions allowed
No tumor in a location where enlargement could cause airway obstruction

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% (> 10 years of age) or Lansky PS 70-100% (≤ 10 years of age)
Life expectancy ≥ 12 weeks
ANC > 500/mm³
Platelet count > 20,000/mm³
Bilirubin < 3 times upper limit of normal (ULN)
AST < 5 times ULN
Creatinine < 3 times ULN
No cardiomegaly or bilateral pulmonary infiltrates on chest radiograph
No oxygen requirement, as defined by pulse oximetry of > 90% on room air
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No history of hypersensitivity reactions to murine protein-containing products
No known sensitivity to rat monoclonal antibodies

PRIOR CONCURRENT THERAPY:

Recovered from the toxic effects of all prior chemotherapy
More than six weeks since prior and no other concurrent investigational agents or tumor vaccines

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609206

Locations

United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor 713-798-1297
Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Yu-Feng Lin 832-824-4258
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Yu-Feng Lin 832-824-4258

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Study Chair:

Chrystal Louis, MD

Baylor College of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000582400, BCM-H-13149, BCM-NESTLES
Study First Received:	February 1, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00609206 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent neuroblastoma
stage 4S neuroblastoma
disseminated neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma

Study placed in the following topic categories:

Antibodies, Monoclonal
Neuroectodermal Tumors
Antibodies
Neuroectodermal Tumors, Primitive
Immunologic Factors
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Neuroectodermal Tumors, Primitive, Peripheral
Recurrence
Neuroblastoma
Immunoglobulins
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Immunologic Factors
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Pharmacologic Actions
Neuroblastoma
Antibodies, Monoclonal

Neuroectodermal Tumors
Neoplasms
Antibodies
Neoplasms, Germ Cell and Embryonal
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009