Cancer Center

First Pediatric Patients Treated in T cell therapy Clinical Trial (CTL019, formerly CART19)

Promising early results of cell therapy to treat acute lymphoblastic leukemia and other B cell cancers

CTL019, a clinical trial of T cell therapy for patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL), has shown exciting early results for the first patients to be treated.

How CTL019 works

This clinical trial, formerly referred to as CART19, uses immune cells taken from a patient's own blood, called T cells. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. Here is how CTL019 works:

1. The cancerous immune cell. B cells, which are found in the immune system, become cancerous in certain leukemias and lymphomas, such as ALL, NHL and CLL.
2. The healthy immune cell. T cells are the workhorses of the immune system, recognizing and attacking invading disease cells.
3. The problem. Cancerous B cells fly under the radar of immune surveillance, evading detection by T cells.
4. The solution. In this experimental treatment, T cells are collected from a patient, then reengineered in a lab to recognize and attach to a protein that is found only on the surface of B cells. After this reengineering, they are called chimeric antigen receptor T cells. The cells are put back into the patient where they disperse to find cancerous B cells.
5. The result. As the reengineered cells multiply in the body, they attach to and kill the rapidly dividing, cancerous B cells. They remain in the body long after to continue fighting any new cancerous B cells.

Initial results of CTL019

While the numbers of patients treated so far are small — 10 adults with chronic lymphocytic leukemia (CLL), and 2 children with acute lymphoblastic leukemia (ALL) — scientists at The Children’s Hospital of Philadelphia and the University of Pennsylvania have been able to show:

• A patient's modified T cells can survive for many months after administration, and have the ability to grow in the body in large quantities.
• The modified T cells have been able to kill large quantities of ALL or CLL cells in 9 of 12 patients treated.

Scientists at The Children’s Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response.

What children might benefit from CTL019?

CTL019 is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. ALL is the most common childhood cancer. T cell therapy is an option for those patients who have very resistant ALL.

Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients with leukemia that has come back (relapsed) who will not benefit from additional chemotherapy or cannot go to bone marrow transplant.

It is important to note that while early results of this treatment are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.

How to contact us

Review the following options for contacting CHOP about CTL019.

• To schedule an appointment or request a second opinion at CHOP, call 267-426-0762.
• If you have a pediatric patient or family member ages 1 to 21 years with B cell ALL or other B cell malignancies you may call 267-426-0762 or contact the Cancer Center online with questions, comments, feedback or requests for information about CTL019 and other clinical trials.
• If you are an adult patient or family member, please visit the Abramson Cancer Center online to learn more about this study and how to get more information.
• For more information about other open clinical trials at CHOP, search our Clinical Trials Search Tool.

Referring a patient for CTL019 and other clinical trials

Referring physicians and families are encouraged to consider the potential benefits of clinical trials early in the cancer treatment process. In the case of CTL019 and other cell therapies, it is critical that cells are collected from the patient before they are too sick. Also, intensive chemotherapy will decrease the number of normal T cells we need to collect from the patient.

While most childhood cancers are cured by standard treatment protocols, learning about the many new experimental therapies available at CHOP soon after diagnosis may keep more options open for patients who relapse.

More about CTL019 and immunotherapy to treat cancer

Dr. Stephan Grupp leads CTL019 efforts at The Children’s Hospital of Philadelphia. His research builds on an ongoing collaboration with the team that originally designed the CTL019 cells as a treatment for B cell leukemias, and first used the cell therapy against chronic lymphocytic leukemia (CLL) in adults.

Carl H. June, MD, of the Perelman School of Medicine at the University of Pennsylvania, led the research group that announced unprecedented results in August 2011 in treating 3 adult patients with advanced cases of CLL. As of the new publication a total of 12 adult and pediatric patients have been treated using CTL019 cells, 9 patients have responded, and 5 (including two children with ALL) experienced a complete remission.

Dr. Grupp and his colleagues adapted the CTL019 treatment to combat ALL, the most common childhood cancer.

Immunotherapy: a new approach to cancer treatment

Discover Magazine listed the CTL019 trial as one of the top 10 stories of 2011.

The CTL019 therapy represents a new approach to cancer treatment called immunotherapy or cell therapy. The idea behind immunotherapy is to use our bodies’ own immune cells, which fight infection, to kill off cancer cells.

Cancer researchers have spent more than a decade studying immunotherapy as a possible treatment for cancer. Over the years they solved many of the problems associated with this type of treatment, including learning how to induce the cells to recognize cancer and how to grow cells in a lab in way that it would be safe to re-infuse them into patients.

The final hurdle in this research was the most difficult to jump: learning how to engineer a cell that would continue to grow in the body for more than a few days, and then remain in the body for an extended period of time to continue controlling a patient’s disease for the long-term. CTL019 reflects a solution to this last problem, making the trial unique compared to earlier forms of cell therapy.

A side effect of treatment

In using CTL019 cells to treat his first pediatric patient, Dr. Grupp found that the very activity that destroyed leukemia cells also stimulated a highly activated immune response called cytokine release syndrome. The child became very ill and had to be admitted to the intensive care unit.

Dr. Grupp and his team decided to counteract these toxic side effects by using 2 immunomodulating drugs that blunted the overactive immune response and rapidly relieved the child’s treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019treatments for adults as well.

Dr. Grupp presented an abstract describing this treatment of CTL019-associated cytokine release syndrome at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2012.