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Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases


Phase 1
N/A
N/A
Open (Enrolling)
Both
Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Lymphoproliferative Disorder, Nasopharyngeal Carcinoma, Leiomyosarcoma, Severe Chronic Active EBV (SCAEBV)

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Trial Information

Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases


First, we will search our cell bank to see if there is a CTL line that is a match with the
subject and his/her donor. This matching is done using HLA type, which measures 6 proteins
on the cell surface. If HLA type has not been previously checked, we will do a blood draw
(half to one tablespoon) so that this can be done.

These CTL lines have been made at Baylor College of Medicine from donors for other
transplant patients or other normal donors from the National Marrow Donor Program. All
donors have been screened in the same way that we screen blood donors. When the CTL lines
were made, blood was taken from the donors and used to grow T cells. To do this, we first
grew a special type of cells called dendritic cells or monocytes and we put a specially
produced human virus (adenovirus) that carries the LMP genes into the dendritic cells or
monocytes. They were then used to stimulate T cells. This stimulation trained the T cells to
kill cells with LMP on their surface.

We then grew these LMP specific CTLs by more stimulation with EBV infected cells (made from
the same blood). We also put the adenovirus that carries the LMP genes into these EBV
infected cells so that we increased the amount of LMP that these cells had. These EBV
infected cells were treated with radiation so they could not grow. Once we made sufficient
numbers of T cells, we tested them to make sure they kill cells with LMP on their surface
and froze them.

To make sure that these cells won't attack the subject's tissues, we will also test the
cells against his/her own cells, which we will grow in the laboratory.

If the level of circulating T-cells in the patient is relatively high, s/he will receive
one treatment of cyclophosphamide. This drug will decrease the numbers of the patient's own
T-cells before the investigators infuse the LMP-specific cytotoxic T-lymphocytes. If the
patient is already receiving chemotherapy, this may not be needed.

The LMP specific CTLs will be thawed and injected IV over 1-5 minutes. Initially, one dose
of T-cells will be given. If after the first dose, there is a reduction in the size of the
patient's disease, they can receive up to five additional doses of the T-cells if they wish.

This is a dose escalation study, which means that the doses of cells will be increased as
more patients are treated, as long as the lower doses are determined to be safe.

Inclusion Criteria


INCLUSION CRITERIA:

SCREENING:

1. Any patient, regardless of age or sex, with one or more of the following EBV-positive
or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma -
Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma -
Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as
high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy
tissue positive for EBV

2. Karnofsky/Lansky score 50% or more.

3. Informed consent explained to and signed by patient or parent/guardian able to give
informed consent and given a copy.

TREATMENT:

1. Any patient, regardless of age or sex, with one or more of the following EBV-positive
or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma -
Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma -
Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as
high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy
tissue positive for EBV

2. The disease needs to be in one of the following stages: - At diagnosis or in first
relapse AND the patient is unable to receive conventional chemotherapy for his/her
condition. - In second or subsequent relapse. - With residual disease after
autologous, syngeneic or allogeneic HSCT.

3. Life expectancy 6 weeks or more.

4. Tumor tissue is positive for EBV.

5. Karnofsky/Lansky score 50% or more.

6. Bilirubin less than 3 less than upper limit of normal (ULN), AST less than 5 less
than ULN, Hgb greater than 8.0 g/dL and serum creatinine less than 3 less than ULN

7. Pulse oximetry of greater than 90% on room air.

8. If post allogeneic HSCT, patient must not have less than 50% donor chimerism in
either peripheral blood or bone marrow.

9. Clinical status at enrollment to allow tapering of steroids to less than 0.5
mg/kg/day prednisone at time of treatment.

10. Informed consent explained to and signed by patient or parent/guardian able to give
informed consent and given a copy.

11. 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.

EXCLUSION CRITERIA:

SCREENING:

1. Known HIV positivity.

TREATMENT:

1. Currently receiving any investigational agents or have received any tumor vaccines
within previous 4 weeks.

2. Active acute grade III-IV graft-versus-host disease.

3. Severe intercurrent infection.

4. Received alemtuzumab or other anti-T-cell antibody within 28 days.

5. HIV seropositivity.

6. Pregnancy (due to unknown effects of this therapy on a fetus) or lactation.

7. Tumor in a location where enlargement could cause airway obstruction.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Patients with dose limiting toxicities after T-cell infusions

Outcome Description:

To determine the safety of intravenous injections of third-party, partially HLA- matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma)

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Carlos A Ramos, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

H-28361-MALTED

NCT ID:

NCT01447056

Start Date:

February 2012

Completion Date:

February 2021

Related Keywords:

  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Lymphoproliferative Disorder
  • Nasopharyngeal Carcinoma
  • Leiomyosarcoma
  • Severe Chronic Active EBV (SCAEBV)
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Lymphoproliferative disorder
  • Nasopharyngeal carcinoma
  • Leiomyosarcoma
  • EBV Cytotoxic T Lymphocytes
  • Carcinoma
  • Hodgkin Disease
  • Leiomyosarcoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Nasopharyngeal Neoplasms

Name

Location

Texas Children's HospitalHouston, Texas  
The Methodist HospitalHouston, Texas  77030