Administration of Autologous CAR-T CD19 Antigen With Inducible Safety Switch in Patients With Relapsed/Refractory ALL (NCT03016377)
Administration of Autologous CAR-T Cells Targeting the CD19 Antigen and Containing the Inducible caspase9 Safety Switch in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia
🩺 Plain-English Summary (8th-Grade Level)
The body has different ways of fighting infection and disease. No single way is effective at 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 combines both T cells and antibodies to try to create a more effective treatment. This investigational treatment is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD19 antigen (ATLCAR.CD19) 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 genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells makes a piece of an antibody called anti-CD19. This antibody can flow through the blood and can find and stick to leukemia cells because these leukemia cells have a substance on their surface called CD19. Anti-CD19 antibodies have been used to treat people with leukemia but have not been strong enough to cure most patients. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood a piece of it is now joined to the surface of the T cells. Only the part of the antibody that sticks to the leukemia 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 CD19 chimeric (combination) receptor-activated T cells 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. Preliminary results of giving ATLCAR.CD19 cells to leukemia patients have been encouraging; however, many subjects receiving this treatment have experienced unwanted side effects including neurotoxicity and/or cytokine release syndrome (also referred to as cytokine storm or an infusion reaction). Cytokines are small proteins that interreact as e signals to other cells and are the way cells talk to one another. During cytokine release syndrome, too many cytokines are released and too many cells in your body react to their release. Symptoms resulting from cytokine release syndrome vary from flu-like symptoms to more severe side effects such as cardiac arrest, multi-system organ failure or death. We predict that about 50% of patients on this study will experience mild to severe cytokine release syndrome. To help reduce cytokine release syndrome symptoms in future patients, a safety switch has been added to the ATLCAR.CD19 cells that can cause the cells to become dormant or "go to sleep". The safety switch is called inducible caspase 9 or iC9. The modified ATLCAR.CD19 cells with the safety switch are referred to as iC9-CAR19 cells. The purpose of this study is to determine whether receiving the iC9-CAR19 cells is safe and tolerable (there are not too many unwanted effects). Researchers has previously tested different doses of the iC9-CAR19. An effective dose that had the least number of unwanted side effects in patients was identified. It was planned to test this dose in more patients to learn more about its effect in the body. This type of research study is called a dose expansion study. It will allow the investigators to collect more information about the effect of this dose in treating of certain type of cancer.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (16 items) and avoid the listed exclusions (56 items).
Location: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill — Chapel Hill, North Carolina
Age range: 3 Years to 70 Years
🧪 Interventions in This Study
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- Exclusion Criteria for Cell Procurement Subjects meeting any of the following criteria cannot be enrolled in this study:
- Subjects with relapsed fulminant CD19+ ALL that is rapidly progressing with circulating lymphoblasts that are rising in proportion to \>50% of circulating white blood cells.
- Intrathecal chemotherapy will be allowed to continue between cell procurement and lymphodepleting chemotherapy.
- Pregnant or breastfeeding (Note: breast milk cannot be stored for future use if the milk is collected while the mother is being treated on study).
- Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Subjects must not have tumor in a location where enlargement could cause airway obstruction.
- Subjects may not have an oxygen requirement as defined by pulse oximetry of \<90% on room air.
- Subjects must not have left ventricular ejection fraction of \<40% (shortening fraction \<27% for pediatric subjects) as measured by echocardiogram or MUGA.
- Patients with the following systemic viral infections will be excluded: active HIV, HBV, HCV. Only subjects meeting the criteria as so described will be infused. Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for Hepatitis B surface antigen, or negative for HCV antibody or HCV viral load
- Patients who are on treatment for other active uncontrolled infections (not referenced above) with resolution of signs/symptoms are not excluded. Non-influenza, non-RSV, isolated upper respiratory infections are not excluded. Other active uncontrolled infections will be excluded.
- Prior to procurement current use of systemic corticosteroids at doses ≥10 mg/day prednisone or its equivalent; those receiving \<10 mg/day may be enrolled at discretion of investigator. (Note: Corticosteroid use with doses at the discretion of the treating physician are allowed after procurement up to the beginning of lymphodepletion. Corticosteroid use is contraindicated following iC9-CAR19 infusion unless medically necessary e.g., to treat CRS).
- Physiologic replacement with hydrocortisone is allowed at doses 6-12 mg/m2/day, or equivalent.
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (1 Sites)
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill — Chapel Hill, North Carolina
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.
- 💵 Compensation indicated: Lymphodepleting Regimen Subjects will receive a lymphodepleting regimen of fludarabine 25 mg/m2/day administered IV over 30 min for three consecutive days and a single IV dose of cyclophosphamide ...
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Explore by condition: All Acute Lymphoblastic Leukemia clinical trials
💡 How to Participate
- Check the checklist above to see if you may qualify.
- Review the official NIH record below to find the coordinating site.
- Ask about the visit schedule, what is covered at no cost, and any travel support.
- Confirm with your own doctor before making a decision.