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Administration of Rapidly Generated LMP, BARF1 And EBNA1 Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Lymphoma


Phase 1
N/A
N/A
Open (Enrolling)
Both
Hodgkin's Disease, Non-Hodgkin's Lymphoma, Lymphoproliferative Disease, Lymphoma

Thank you

Trial Information

Administration of Rapidly Generated LMP, BARF1 And EBNA1 Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Lymphoma


Earlier subjects gave blood for us to make LMP/BARF1/EBNA-1 (GRALE) CTLs in the lab. These
cells were grown and frozen for the subject.

The GRALE T cells will then be thawed and injected into the subject over 2-10 minutes. The
subject may be pretreated with Tylenol and Benadryl. These are given to prevent a possible
allergic reaction to the GRALE T cell administration. Initially, two doses of GRALE T cells
will be given 2 weeks apart.

Patients will be started on the lowest dose (1 of 3 different levels) of GRALE T cells. Once
that dose schedule proves safe, the next group of patients will be started at a higher dose.
This process will continue until all 3 dose levels are studied. If the side effects are too
severe, the dose will be lowered or the GRALE T cell injections will be stopped.

If after the 2nd infusion there is a reduction in the size of the lymphoma on CT or MRI scan
as assessed by a radiologist, the subject can receive additional doses of the GRALE T cells
if they wish (up to 6 times). Follow up testing will be collected just as it had from the
1st infusion. CT scans, MRI, or nuclear imaging will be collected 1-3 months after the final
infusion.

All of the treatments will be given by the Center for Cell and Gene Therapy at Texas
Children's Hospital or the Methodist Hospital.

We will follow the subjects after the injections. They will either be seen in the clinic or
the subject will be contacted by a research nurse yearly for 5 years. To learn more about
the way the T cells are working in the body, an extra 20-50 mls (4-10 teaspoons) of blood
will be taken before each infusion and then at 2,4 and 6 weeks and 3,6,9 and 12 months after
each infusion (8 times). The blood may be drawn from the central line at the time of the
regular blood tests. We will use this blood to see how long the GRALE T cells last and to
look at the immune response to the subjects cancer.

One additional blood sample might be drawn 3 to 4 days after the infusion. Please let the
doctor know if it will be difficult to come in for this blood draw on Day 3 to 4.

Subjects will be on study for approximately 5 years. If they receive additional doses of the
GRALE T cells as described above, they will be followed until 5 years after the last dose of
GRALE T-cells.

Inclusion Criteria


Inclusion Criteria at time of Procurement

Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's
Lymphoma, (regardless of the histological subtype) or EBV
(associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV)

In second or subsequent relapse (or first relapse or with active disease if
immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission
who have a high risk of relapse) OR any patient with primary disease or in first remission
if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin
disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a
Richter's transformation of CLL. (Group A)

OR

In remission or with minimal residual disease status after autologous or syngeneic stem
cell transplantation (SCT). (Group B)

- EBV positive tumor

- Weighs at least 12kg

- Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.

Inclusion Criteria at time of Infusion

Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's
Lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative
disease or Severe Chronic Active EBV (CAEBV) and

In second or subsequent relapse (or first relapse or with active disease if
immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission
who have a high risk of relapse) OR any patient with primary disease or in first remission
if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin
disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a
Richter's transformation of CLL. (Group A)

OR

In remission or with minimal residual disease status after autologous or syngeneic SCT.
(Group B)

- EBV positive tumor (can be pending at this time)

- Patients with life expectancy > 6 weeks.

- Patients with bilirubin < 3x upper limit of normal, AST < 5x upper limit of normal,
and Hgb > 8.0 (may be a transfused value).

- Patients with a creatinine < 2x upper limit of normal for age

- Pulse oximetry of > 90% on room air

- Patients should have been off other investigational therapy for 4 weeks prior to
entry in this study.

- Patients with a Karnofsky/Lansky score of > 50

- Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.

- Informed consent explained to, understood and signed by patient/guardian.
Patient/guardian given copy of informed consent.

- CAEBV is defined as patients with high EBV viral load in plasma or PBMC (> 4000
genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV

Exclusion Criteria at Time of Procurement

- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)

Exclusion Criteria at Time of Infusion

- Pregnant or lactating

- Severe intercurrent infection.

- Current use of systemic corticosteroids > 0.5 mg/kg/day

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Assessment of toxicity of escalating doses of LMP, BARF1 and EBNA1 CTLs

Outcome Description:

To determine the safety of escalating doses of 2 intravenous injections of autologous rapid LMP, BARF1 and EBNA1 specific cytotoxic T-lymphocytes (CTL) in patients with EBV-associated Hodgkin's Disease or non-Hodgkin's lymphoma or T/NK-lymphoproliferative disease and CAEBV.

Outcome Time Frame:

8 weeks

Safety Issue:

Yes

Principal Investigator

Helen E Heslop, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

BCM

Authority:

United States: Food and Drug Administration

Study ID:

H-29617-GRALE

NCT ID:

NCT01555892

Start Date:

January 2013

Completion Date:

December 2020

Related Keywords:

  • Hodgkin's Disease
  • Non-Hodgkin's Lymphoma
  • Lymphoproliferative Disease
  • Lymphoma
  • EBV
  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Lymphoma Relapse
  • Autologous or Syngeneic Stem Cell Transplant
  • T/NK-lymphoproliferative disease
  • LMP
  • BARF1
  • EBNA1
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders

Name

Location

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