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| Sponsor: | Baylor College of Medicine |
|---|---|
| Collaborators: |
Texas Children's Hospital The Methodist Hospital System Center for Cell and Gene Therapy, Baylor College of Medicine |
| Information provided by (Responsible Party): | catherine bollard, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00058617 |
Purpose
Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. The investigators want to see if they can grow special white blood cells, called T cells, that have been trained to kill EBV infected cells and then give them back to the patient. To find out how long these cells last the investigators may put a marker gene into them so they can track them. Gene marking is optional in this study. Eligible patients can participate without the gene marking if they choose.
The purpose of this study is to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease and non-Hodgkins Lymphoma.
| Condition | Intervention | Phase |
|---|---|---|
|
EBV Positive Hodgkins Disease EBV Positive Non-Hodgkins Lymphoma EBV Positive Plasma Cell Neoplasm |
Procedure: Injection of EBV Specific Cytotoxic T-Lymphocytes |
Phase I |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | The Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma. |
| Estimated Enrollment: | 18 |
| Study Start Date: | January 1996 |
| Estimated Study Completion Date: | December 2014 |
| Primary Completion Date: | February 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Patient
Patients with Hodgkin disease or non-Hodgkin Lymphoma or plasma cell neoplasms in second or subsequent relapse in whom the EBV genome or antigens have been demonstrated in tissue biopsies.
|
Procedure: Injection of EBV Specific Cytotoxic T-Lymphocytes
Each patient will receive two injections, 14 days apart, according to the following dosing schedules: Group One Day 0 2x107 cells/m2 Day 14 2x107 cells/m2 Group Two Day 0 2x107 cells/m2 Day 14 1x108 cells/m2 Group Three Day 0 1x108 cells/m2 Day 14 2x 108 cells/m2 If patients with active disease have stable disease or a partial response by the RECIST criteria at their 8 week or subsequent evaluations they are eligible to receive up to 6 additional doses of CTLs at monthly intervals-each of which will consist of the same cell number as their second injection. Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion. |
The investigators will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95. The investigators will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. The investigators will then test the T cells to make sure that they kill the EBV infected cells and not normal cells and freeze them.
Patients will be entered into one of three different dosing schedules being evaluated. Three to six patients will be evaluated on each dosing schedule. Escalation will continue until irreversible or life threatening side effects considered to be related to the T cells are seen.
For patients who agree to gene marking (this is optional), the investigators will mark these cells with a special bacterial marker gene. The investigators will use a mouse virus (retrovirus) that has been changed to stop it from causing infection. The marker, a gene called Neo, is put inside this special virus.
The cells will be injected into the patients' vein over 10 minutes, after pretreatment with Tylenol and Benadryl. Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration. A total of two doses will be given two weeks apart. All of the treatments will be given at Texas Children's Hospital or The Methodist Hospital.
Patients will be followed in the clinic after the injections. At each visit about 10ml (2 teaspoonfuls) of blood will be taken every other week for 6 weeks after the injection and then every 3 months for 1 year to monitor the patients' blood chemistry and hematology.
For patients who agreed to gene marking, an extra 8 teaspoons (40 mls) of blood will be taken before each infusion, 24 hours after each infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at 3, 6, 9 and 12 months post infusion) then once every 6 months for the first 5 years and then yearly thereafter for the next 10 years. The investigators will use this blood to test for the frequency and activity of EBV specific T cells. That is, to learn more about the way the T cells are working and how long they last in the body.
The investigators will also use this blood to see if there are any long term side effects of gene transfer. Patients who received cells that have a marker gene will need to be followed (seen in clinic or contacted by a research nurse) at least every six months for the next five years and then yearly thereafter for the next ten years so the investigators can see if there are any long term side effects of the gene transfer.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. 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 CCGT Protocol Review Committee and the FDA reviewer.
Contacts and Locations| United States, Texas | |
| Texas Children's Hospital | |
| Houston, Texas, United States, 77030 | |
| The Methodist Hospital | |
| Houston, Texas, United States, 77030 | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| Study Chair: | Helen Heslop, M.D. | Baylor College of Medicine |
More Information
| Responsible Party: | catherine bollard, MD, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00058617 History of Changes |
| Obsolete Identifiers: | NCT00002821 |
| Other Study ID Numbers: | 6423-ANGEL, Angel |
| Study First Received: | April 8, 2003 |
| Last Updated: | December 20, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
Neoplasms Hodgkin Disease Lymphoma Lymphoma, Non-Hodgkin Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders |
