Administration of T Lymphocytes for Prevention of Relapse of Lymphomas
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02663297|
Recruitment Status : Active, not recruiting
First Posted : January 26, 2016
Last Update Posted : March 3, 2022
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 disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria 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. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration.
In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD30. This antibody floats around in the blood and can detect and stick to cancer cells called lymphoma cells because they have 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 part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant. This is the first step in determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help them. The researchers also want to find out what side effects patients will have after they receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in your body.
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Disease Lymphoma Lymphoma, Non-Hodgkin Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type||Drug: ATLCAR.CD30 cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Prevention of Relapse of CD30+ Lymphomas After High Dose Therapy and Autologous Stem Transplantation (ATLAS)|
|Actual Study Start Date :||July 15, 2016|
|Actual Primary Completion Date :||January 15, 2021|
|Estimated Study Completion Date :||January 2037|
Experimental: ATLCAR.CD30 cells
Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10^7 cells/m^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10^8/m^2) given in the same trial.
Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.
Drug: ATLCAR.CD30 cells
Three dose levels will be evaluated:
Group One, 2x10^7 cells/m^2 (maximum dose 5x10^7 cells)
Group Two, 1x10^8 cells/m^2 (maximum dose 2.5x10^8 cells)
Group Three, 2x10^8 cells/m^2 (maximum dose 5x10^8 cells)
Other Name: CAR.CD30 T cells
- 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 ]Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and cytokine release syndrome (CRS) toxicity will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of dose-limiting toxicity
- To measure the survival of ATLCAR.CD30 in vivo [ Time Frame: 15 years ]Persistence of CAR.CD30 T cells in vivo will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples
- To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse [ Time Frame: 15 years ]PFS is defined from day of ASCT to relapse (in subjects with a documented complete response after ASCT) or progression (in subjects with documented stable disease or partial response after ASCT), or death as a result of any cause as per the Revised Response Criteria for Malignant Lymphoma
- Determine the overall survival after infusion of ATLCAR.CD30 [ Time Frame: 15 years ]Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02663297
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Wake Forest University|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator:||Natalie Grover, MD||Clinical Director of Cellular Therapy Program|