Administration of T Lymphocytes for Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (CART CD30)
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if they can attach a gene to T cells that will help them do a better job at recognizing and killing lymphoma cells.
The new gene that investigators will put in T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients.
For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way, it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown.
|Non-Hodgkin's Lymphoma Hodgkin's Lymphoma||Drug: CAR.CD30 T cells||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma (CART CD30)|
- Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes [ Time Frame: 6 weeks ]To evaluate the safety of escalating doses of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CAR.CD30) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
- Measure the survival of CAR.CD30 in vivo [ Time Frame: 15 years ]To measure the survival of CAR.CD30 transduced ATL in vivo.
- Measure the response of the subjects tumor to the CAR.CD30 transduced ATL [ Time Frame: 15 years ]To measure the anti-tumor effects of CAR.CD30 transduced ATL in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
|Actual Study Start Date:||October 3, 2011|
|Estimated Study Completion Date:||December 2031|
|Primary Completion Date:||January 28, 2016 (Final data collection date for primary outcome measure)|
Experimental: CAR.CD30 T cells
Three dose levels will be evaluated. Using the modified continual reassessment method, cohorts of size two will be enrolled at each dose level. Each patient will receive one injection (IV) according to the dosing schedules: starting with the lowest cell dose (2×10^7 cells/m2) and then escalate the cell dose to the highest cell dose (2×10^8/m2) as per study design.
Drug: CAR.CD30 T cells
Three dose levels will be evaluated:
Group One, 2x10^7 cells/m^2
Group Two, 1x10^8 cells/m^2
Group Three, 2x10^8 cells/m^2;
Cell Administration: CAR+ ATL will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc.
When the patient enrolls on this study, they will be assigned a dose of CD30 chimeric receptor-activated T cells. The dose level of cells that they will receive will not be based on a medical determination of what is best for the patient, instead the dose is based on the order in which the patient enrolled on the study relative to other participants. Subjects enrolled earlier in the study will receive a lower dose of cells than those enrolled later in the study. The risks of harm and discomfort from the study treatment may bear some relationship to the dose level. The potential for direct benefit, if any, may also vary with the dose level.
The patient will be given an injection of CD30 chimeric receptor-activated T cells into the vein through an IV line at the assigned dose. The injection will take 1-10 minutes. Investigators will follow the subject in the clinic after the injection for up to 4 hours.
To learn more about the way the CD30 chimeric receptor-activated T cells are working and how long they last in the body, extra blood will be drawn.
If the patient has stable disease (the lymphoma did not grow) or there is a reduction in the size of the lymphoma on imaging studies after the T-cell infusion, s/he can receive up to six additional doses of the T cells at 8 to 12 weeks intervals if s/he wishes. After each T-cell infusion, s/he will be monitored as described above.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316146
|United States, North Carolina|
|University of North Carolina Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Barbara Savoldo, MD, PhD||University of North Carolina, Chapel Hill|