CTL019 is a clinical trial of T cell therapyfor 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). At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patientson this trial.

In July 2014, CTL019 was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In this clinical trial, immune cells called T cells are taken from a patient's own blood. 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. This is how T cell therapy works:

30 patients with acute lymphoblastic leukemia (25 children and 5 adults) have been treatedusing T cell therapy.Of those patients:

The most recent results were published in The New England Journal of Medicine in October 2014. Scientists at The Childrens 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, and because those patients have been followed for a relatively shorttime,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, and maintain that response.

At this point CHOP's capability to enroll patients is limited because of the need to manufacture the T cell product used in this therapy. Our goal is to boost enrollment soon, by increasing our manufacturing capabilities and by broadening this study to other pediatric hospitals.

T cell therapy 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. It 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 whose leukemia is not responding to chemotherapy,and whose disease has come back after a bone marrow transplant.

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

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.

Stephan Grupp, MD, PhD, leads CTL019 efforts at The Childrens 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.

Richard Aplenc, MD, PhD, MSCE, and Susan Rheingold, MD,are the first points of contact for any pediatric patient considering T cell therapy,andwill help families navigate the process of coming to CHOP for a second opinion. These CHOP oncologists are among the nation's leading experts in pediatric leukemia.

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 three adult patients with advanced cases of CLL.

Dr. Grupp and his colleagues adapted the CTL019 treatment to combat ALL, the most common childhood cancer. Initial results of this clinical trial were published by The New England Journal of Medicine on March 25, 2013.

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 patients disease for the long-term. CTL019 reflects a solution to this last problem, making the trial unique compared to earlier forms of cell therapy.

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 two immunomodulating drugs that blunted the overactive immune response and rapidly relieved the childs treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019 treatments 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.

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T Cell Therapy (CTL019) | The Children's Hospital of ...

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