Non-Hodgkin Lymphoma Clinical Trial
Official title:
Administration of LMP1- and LMP2- Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma or Chronic Active EBV Infection (ALDI)
The purpose of this study is to obtain blood (up to 90 ml or 18-teaspoonfuls on one or two
occasions) to make LMP1- and LMP2-cytotoxic T-lymphocytes and grow them in the laboratory in
such a way that they are able to attack LMP1- and LMP2-positive cells in the laboratory.
If we are successful in growing these cells and if we feel they would be helpful to the
donor, we would then give the cells back to the donor.
This trial is for patients that have a type of lymph gland cancer called Hodgkin or
non-Hodgkin lymphoma, or chronic active Epstein Barr virus (EBV) infection, which has come
back or not gone away after treatment, including the best treatment we know.
This is a research study using special immune system cells called LMP1- and LMP2-specific
cytotoxic T lymphocytes (LMP1- and LMP2-CTLs), a new experimental therapy. As in chronic
active EBV infection, some patients with Hodgkin or non-Hodgkin lymphoma show evidence of
infection with the virus that causes infectious mononucleosis (EBV) before or at the time of
their diagnosis of the Lymphoma. EBV is found in the cancer cells of up to half the patients
with lymphoma, suggesting that it may play a role in causing lymphoma. The cancer cells
infected by EBV are able to hide from the body's immune system and escape destruction. We
want to see if special white blood cells, called T cells, that have been trained to kill EBV
infected cells can survive in the patient's blood and affect EBV-positive cells. In this
present study we are trying to find out if we can improve this treatment by growing T cells
that only recognize two of the proteins expressed on lymphoma cells called LMP1 and LMP2.
These special T cells are called LMP1- and LMP2-specific cytotoxic CTLs.
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 used 40, 400ug/kg over 6 to 8
hrs daily x 4 given as daily intravenous infusions that will be completed 48-72 hours prior
to CTL infusion. Patients will be premedicated prior to CD45 infusions and monitored as per
the SOP for CD45 MAbs infusion.
Day 1 through Day 4: YTH 24/54 400ug/kg over 6 to 8 hr; Day 5: Rest; Day 6, 7 or 8: CTL
Infusion (provided CD45 Mab level <100 ng/ml)
Preparation of the Patient:
Oxygen and suction equipment must be available in the room. Emergency drugs (Benadryl,
Epinephrine, solucortef to solumedrol) in appropriate doses must be preordered by the
physician prior to initiation of each infusion with doses available. A code card containing
the appropriate doses of each medicine according to the patient's weight will also be
available. Continuous telemetric monitoring by pulse oximeter and EKG will begin prior to
and for 6 hours after each antibody infusion has taken place. Baseline vital signs are taken
and recorded and monitored as per the SOP for antibody infusions.
MAbs Infusion:
The antibody aliquot to be infused will arrive in the treatment area hand-carried by the
attending physician or appointed designate.
The antibody aliquot will be diluted in minimal amounts of normal saline. The resulting
solution is stable for 24 hours.
The antibody solution is administered by a syringe pump in incremental doses, 0.2-0.8 mg in
the first hour and up to 10 mg/hr thereafter, for a maximum infusion time of 8 hrs. A
registered nurse and a physician must be readily available
Antibody toxicity:
Volume Overload: This is of particular importance in small recipients and will be monitored
carefully.
Inflammatory mediator release from damaged circulating white cells and allergic reactions:
Fever, chills, rigors, pruritis, urticaria, nausea, vomiting, throat tightness and dyspnea
may occur. These reactions usually respond to slowing or stopping the infusion and/or the
parenteral administration of diphenhydramine, hydrocortisone, meperidine or anti-emetics.
Administration of O2, epinephrine, bronchodilators or IPPB may be necessary.
Adverse effects of CD45 MAbs on CTL Our experience to date has shown rapid clearance of CD45
MAbs from the plasma, such that levels are undetectable by 24-48hrs after infusion. However,
the MAb levels will be measured before CTL infusion and if free plasma CD45 MAbs are present
CTL infusion will be deferred for 24 hours
CTL Infusion:
Dose Levels of CTLs: The following dose levels will be evaluated: Each patient will receive
1 injection, according to the following dosing schedules:
Dose level I: 2 x 10e7 cells/m2; Dose level II: 1 x 10e8 cells/m2; Dose level III: 3 x 10e8
cells/m2; Dose level IV: 1 x 10e9 cells/m2. Patients will be pre-medicated with Benadryl
1mg/kg IV (max 50mg) and Tylenol 10mg/kg po (max 650mg).
Cell Administration: LMP1- and LMP2-specific T cells will be given by intravenous injection
over 1-10 minutes through either a peripheral or a central line.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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