Lmp1 and Lmp2 Specific CTLs Following Cd45 Antibody for Relapsed Ebv-Positive Hodgkin's Or Non-Hodgkin's Lymphoma (ALDI)
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|ClinicalTrials.gov Identifier: NCT00383097|
Recruitment Status : Terminated (The trial was terminated in 2010 due to lack of enrollment.)
First Posted : October 2, 2006
Last Update Posted : May 24, 2012
|First Submitted Date ICMJE||September 28, 2006|
|First Posted Date ICMJE||October 2, 2006|
|Last Update Posted Date||May 24, 2012|
|Start Date ICMJE||September 2006|
|Primary Completion Date||February 2010 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00383097 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Lmp1 and Lmp2 Specific CTLs Following Cd45 Antibody for Relapsed Ebv-Positive Hodgkin's Or Non-Hodgkin's Lymphoma|
|Official Title ICMJE||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.
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 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
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Completion Date||February 2010|
|Primary Completion Date||February 2010 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Diagnosis of EBV-positive Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL; all histological subtypes except Burkitt's lymphoma), or EBV (associated)-T/NK-LPD, or chronic active EBV infection (CAEBV) after second or subsequent relapse including after autologous or syngeneic stem cell transplant (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated). CAEBV is defined as i) illness for greater than 3 months duration (EBV-related illness or symptoms including fever, persistent hepatitis, extensive lymphadenopathy, or hepatosplenomegaly); ii) increased amounts of EBV-DNA in peripheral blood (equal or greater than 400 genome copies per ug of DNA) or abnormal high levels of EBV antibodies (VCA IgG equal or greater than 1:5120 or EA IgG equal or greater than 1:640; and iii) no evidence of previous immunological abnormalities or other recent infection that might explain the observed condition.
Patients with life expectancy greater than 6 weeks.
Patients with a Karnofsky score (age ≥16) of greater than 50 or Lansky score (age<16) of greater than 50
No severe intercurrent infection.
HIV negative donor (if autologous donor, patient must be HIV negative)
Patient, parent/guardian able to give informed consent.
Patients with bilirubin less than3 x normal, AST less than 5 x normal, and Hgb greater than 8.0
Patients with a creatinine less than 2 x normal for age
Patients should have been off other investigational therapy including T cell therapies for one month prior to entry in this study.
Female patients with reproductive capacity must have a negative pregnancy test. Women of childbearing potential must not be pregnant and must be on effective birth control. 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 CAGT Protocol Review Committee and the FDA reviewer.
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.
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00383097|
|Other Study ID Numbers ICMJE||19275
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Stephen Gottschalk, Baylor College of Medicine|
|Study Sponsor ICMJE||Baylor College of Medicine|
|PRS Account||Baylor College of Medicine|
|Verification Date||May 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP