Study of LMP1- and LMP2- Specific Cytotoxic T-Lymphocytes (CTL)

NCT00515957 | Withdrawn Phase 1 DMC

• 2 other identifiers: 2099620996-DELLA
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study NPC patient will receive 4 days of treatment with CD45 antibody followed by one dose of LMP1- and LMP2-CTL. From this, we can learn if treating the patient first with the CD45 antibody will also let LMP1- and LMP2-CTL we give grow better. In addition, we will find out, if LMP1- and LMP2-CTL are safe and have enhanced anti-tumor activity in comparison to standard EBV-CTL. This study aims to determine the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (MAb) in patients with EBV-positive nasopharyngeal carcinoma (NPC). And to obtain information on the expansion, persistence and anti-tumor effects of autologous LMP1- and LMP-2 specific CTL given after lymphodepletion with CD45 MAb in patients with EBV-positive NPC.

Conditions

NASOPHARYNGEAL CARCINOMA

Outcome Measures

Primary Outcomes (1)

• To determine the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (MAb) in patients with EBV-positive nasopharyngeal carcinoma (NPC).

  12 months

Secondary Outcomes (1)

• To obtain information on the expansion, persistence and anti-tumor effects of autologous LMP1- and LMP-2 specific CTL given after lymphodepletion with CD45 MAb in patients with EBV-positive NPC.

  12 months

Study Arms (1)

Patients

EXPERIMENTAL

Patients with Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV-genome or antigens have been demonstrated in tissue biopsies

Genetic: genetically modified CTLs in combo with CD45 antibodies

Interventions

genetically modified CTLs in combo with CD45 antibodies GENETIC

LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (MAb). --Infusions of CD45 MAbs: A fixed dose of CD45 MAbs will be used determined from our previous and ongoing studies in stem cell transplant recipients will be used43, 400ug/kg over 6 to 8 hrs daily x 4 given as 4 daily intravenous infusions that will be completed 48-72 hours prior to CTL infusion. Day 1 YTH 24/54 400ug/kg over 6 to 8 hr 2 YTH 24/54 400ug/kg over 6 to 8 hr 3 YTH 24/54 400ug/kg over 6 to 8 hr 4 YTH 24/54 400ug/kg over 6 to 8 hr 5 Rest 6-8 CTL Infusion (provided CD45 MAb level \<100 ng/ml) --LMP1- and LMP2-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. 2x 10\^7 cells/m2 1x 10\^8 cells/m2 3 x 10\^8 cells/m2 1 x 10\^9 cells/m2

Patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive) in whom the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial.
• Any patient with EBV positive NPC, in relapse or with primary resistant disease
• Patients with a life expectancy 6 weeks or greater.
• Patients with a Karnofsky score (age at least 16; for Karnofsky scale see full protocol) or Lansky score (less than 16; for Lansky scale see full protocol) of 50 or greater as described below:
• Patients with bilirubin \<2x normal, SGOT \<3x normal, and Hgb greater than 8.0.
• Patients with a creatinine 2x normal or less for age.
• Patients should have been off other investigational therapy for one month prior to entry in this study.
• Patient, parent/guardian able to give informed consent.

You may not qualify if:

• Severe intercurrent infection.
• Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.
• Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator¡-s discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Stephen Gottschalk, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2007
• First Posted: August 14, 2007
• Study Start: August 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: April 16, 2012

Record last verified: 2012-04