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)
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.
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
Volume Overload: This is of particular importance in small recipients and will be monitored
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
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
Dose limiting Toxicity: Two patients in each cohort are followed
6 weeks post CTL infusion
MALCOLM K BRENNER, MD
Center for Cell and Gene Therapy, Baylor College of Medicine
United States: Food and Drug Administration
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|