T Cell Therapy for Acute Lymphoblastic Leukemia

CTL019 is 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). At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patients on this trial. 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.


T- Cell Therapy

Nicholas Wilkins: I was playing football with my friends and like, I was getting really tired really quickly, and I was like I guess I'm just out of shape. But then they said that the cancer had come back and I was kind of like really shocked at that.

John Wilkins: After Nicholas relapsed and he didn't respond to the chemo therapy after his first bone marrow transplant, we're kind of in a state of limbo, which is always really torturous for any parent with a child that's being treated for cancer because we didn't have a direction to go in to fight the cancer.

Stephan Grupp, MD, PhD: So, what we're trying to do is develop a new way of targeting cancer. And the idea is that there are cells in your body, cells called T-cells, which are cells of your immune system. T-cells could actually attack cancer, but they never do.

Nicholas Wilkins: He said that he was conducting a new study that would take T-cells out of my body and kind of engineer them to go after the cancer cells and destroy them.

Stephan Grupp, MD, PhD: And so, what we're trying to do was to make the T-cells, which can be very powerful against cancer, to go after cancer cells. Our group has used a method of making T-cells that was developed at the University of Pennsylvania. What we do, is we collect T-cells from the patient. We take those T-cells and then we put those T-cells in a lab. We exposed those T-cells to a virus. The virus genetically engineers the T-cells and that makes the T-cells go after the cancer cells. The T-cells then grow in the lab to a very large number. After they go into the patient, they essentially go everywhere in the body that there could be a cancer cell, seek out those cancer cells and destroy them.

This is completely different from chemo therapy. This is a totally different idea, which is really harnessing the power of the immune system to go after cancer in an extremely targeted way. So, it is classic personalized medicine. We're taking the patient's own cells, we are genetically engineering them to go after the patient's specific cancer.

Our clinical trial is treating a disease called acute lymphoblastic leukemia, which is a disease that happens in both adults and children and is the most common cancer in children. Emily Whitehead was the first pediatric patient to receive this cell therapy ever. She is a little girl who had leukemia that had come back and she had no treatment options. We have treated a total of 27 patients with acute lymphoblastic leukemia. Five of those patients are adults and the other 22 patients are kids. A total of 24 out of the 27 — 89 percent — have gone into a complete remission. A complete remission does not guarantee long-term control of disease because there can be cells hiding that our tests don't see. Five out of the 24 who had complete responses experienced a recurrence of their disease and the rest have not.

Tom Whitehead: I believe it was May 10 of 2012, they checked her bone marrow, that's when Dr. Grupp told us that it worked.

Kari Whitehead: Emily is doing amazing. She is in third grade. She was able to keep up with her class, so she's still in school with her school mates. She's at the top of her class. She's just, she's really just, It's almost like if you didn't know what happened to her, you — and saw her now — you would have no idea what she's has been through.

Stephan Grupp, MD, PhD: We need to follow these patients for longer to really know what our ability to keep these patients in remission for the long term is.

Lisa Wilkins: Nicholas had his infusion in May of 2013, so just six months ago.

John Wilkins: After we got the results that showed he didn't have cancer in his bone marrow or blood, we're ecstatic but we're also very cautious, but we're very hopeful.

Nicholas Wilkins: He says my bone marrow looks great and that it looks like no cancer cells are in there, and that the T-cells are doing their job. Since the T-cell therapy, I've gotten back into my groove of playing football with my friends.

Stephan Grupp, MD, PhD: Most children with this kind of leukemia are successfully treated with chemo therapy. Those kids don't need this therapy. However, if a patient experiences recurrence with their disease, it's probably worthwhile having your doctor speak to us and see what role this treatment might play.

John Wilkins: He's got the standard risk ALL and each time it's come back after the first treatment, it came back the same.

Lisa Wilkins: They don't really know why it’s come back. His home doctors basically think that his B cells, which have the leukemia, somehow were able to somehow go into hiding each time and then came back each time. So, they don't really know why. That's really the big question for us. His doctors brought up the fact that he really had no other options at that point and then he brought up CHOP, and said that there was an experimental T-cell study and that's where they wanted to send us.

Stephan Grupp, MD, PhD: Since we have to collect cells from patients, we have to collect those cells at a time when the patients have enough cells to actually collect, and if you get more and more chemo therapy for recurrent disease, it gets harder and harder to collect those cells. So, we found that an early discussion between the patient's oncologist and our group here at CHOP has been incredibly helpful in getting this for patients who actually need it.

So, right now, we're able — between our ability to make the cells and our ability to treat the patients — we're able to treat about two or three patients a month. In order to have a lot more patients than that treated, we really are going to have to open this at other hospitals.

So the next step is to work with a drug company that has licensed this technology, the drug company Novartis, and do a pediatric trial at multiple pediatric hospitals. The other incredibly exciting thing is that this is a treatment, that this drug company, Novartis, is interested in actually making a true FDA-approved drug, and the first thing that they want actually be approved for this drug is pediatric acute lymphoblastic leukemia. Drug companies typically don’t go to a pediatric indication for their first treatment indication. In this situation, they're actually going to pediatrics first, and I am very, very excited about that.

Tom Whitehead: Our number one hope every day is that those T-cells keep working for Emily and keep her in remission, and the ultimate goal is to wipe out childhood cancer altogether.

Stephan Grupp, MD, PhD: So, the group at the University of Pennsylvania and here at CHOP are extremely interested in the question about whether this treatment, this cell therapy treatment, will work as well in diseases other than leukemia. We're working very hard to find other targets in other cancers that we can exploit using the same cell therapy technology, and it's absolutely possible to adapt these cells to go after different cancers, but until you try it in patients, you don't know how well it's going to work. And so, we're extremely interested in knowing whether this might work in other cancers, especially solid cancers that are not like leukemia.

Tom Whitehead: We tell people that we would have taken Emily anywhere in the world that we thought would help her, and we felt very fortunate that all the research that we did led us here to Philadelphia, Pennsylvania, right in our home state where we live. And we tell people that from all over the world, you know, that it's worth the trip here because there's a lot of research being done here, a lot of positive things.

Topics Covered: Acute Lymphoblastic Leukemia (ALL)

Related Centers and Programs: Relapsed Leukemia and Lymphoma Program, Cancer Center