Drug discovered 20 years ago by MCG doctors still providing hope for cancer patients

When Coulter Hnatt of College Station, Texas, was diagnosed with a brain tumor in 2012, his family traveled the country seeking the best care for him in places renowned for treating kids with cancer. It wasn’t until he was virtually out of options that they landed in Augusta, where a therapy based on a discovery there nearly 20 years ago is offering him and others a better quality of life and hope for the future.

 

Coulter, now 9, was among the first to enroll 18 months ago in a phase 1 clinical trial at Children’s Hospital of Georgia that is using immunotherapy with a standard chemotherapy to treat children with brain tumors that have come back after other treatments or are progressing. There are now 26 children enrolled in the trial, 20 in Augusta and six at Children’s Healthcare of Atlanta, with a third site potentially opening soon at Children’s Hospital of Wisconsin in Milwaukee, said Dr. Ted Johnson, national principal investigator for the clinical trial.

The trial uses a drug called Indoximod, which inhibits an enzyme called indoleamine 2,3-dioxygenase or IDO that has been shown to inhibit the function of T cells in the immune system, in conjunction with the brain tumor drug temozolomide and other treatments such as radiation therapy.

The enzyme IDO was first discovered at Medical College of Georgia in 1998 by a team led by Drs. David Munn and Andrew Mellor, who showed it was key to helping a fetus survive in the womb by avoiding attack from the mother’s immune system. Johnson, a physician scientist who trained at MCG and had Mellor as his advisor, helped to establish the link between brain tumors and IDO that the clinical trial is now based upon.

The clinical trial and clinic has gotten a regular boost from Alex’s Lemonade Stand Foundation, including $53,000 last week from its participation in Alex’s Million Mile fundraiser last year. That money is critical for supporting those efforts, Johnson said. Because there are relatively few childhood cancers, most companies are not willing to invest in them first and focus instead on adult cancer clinical trials so that foundation support is crucial, Johnson said.

“You have to look for foundation money, you have to look for philanthropic support,” he said. “We have some donors in the community that are key to our success.”

The trial will move from the Georgia Cancer Center in August to dedicated space in a Clinical Research Unit in the children’s hospital, which the trial currently uses for some lengthy clinic visits.

“These are time consuming complicated, intensive clinic visits,” Johnson said. “All of the patients have different needs that are all very complex. It just isn’t possible to see these phase 1 complicated brain tumor patients in a regular clinic space.”

That included a visit last week with Jazzmyn Smith, 16, of Waynesboro, one of only two local patients in the Augusta arm of the clinical trial. Her mom found her one morning down on the bathroom floor, and a scan later showed she had a brain tumor in an awkward place where it could not be surgically removed without serious brain damage. Chemotherapy did little to slow her tumor and she ended up entering the clinical trial, said her mother, Letitia Johnson.

“Within a week she popped up,” she said, and was able to come off a feeding tube and started looking better.

Jazzmyn is an example of the kind of complex cases the clinical trial sees in that it is not entirely clear what kind of brain tumor she has, Johnson said. It was classified as a low-grade form of one kind of brain tumor but behaved much differently . But that could be one of the strengths of this approach, he said.

“Hypothetically, an effective immunotherapy may be able to work on a wide range of brain tumor types,” Johnson said. “Classically, we have developed therapies for specific types of brain tumors because some of the drugs don’t work on some of the tumors. But with immunotherapy, your immune system only cares that the altered proteins in the tumor shouldn’t be there. So our great hope is we don’t have to restrict this to a single type of brain tumor.”

By using immunotherapy, using the IDO inhibitor to expose the tumor to the immune system, in combination with the brain tumor drug, also allows the researchers to take a different approach to trying to kill the tumor, he said.

“We don’t have to kill every tumor cell. In standard approaches, you would,” Johnson said. For instance, in some particularly difficult to treat brain tumors called glioblastoma, the tumors often spread out in “fingers” in surrounding brain tissue.

“There is no way to cut it out. In most cases you can’t get enough radiation in the places where there is microscopic disease. But that’s exactly what the immune system is made to do. Enlisting the immune system has the potential to go in and mop up these areas of microscopic residual disease.”

The trial has grown so much that a recent $100,000 donation from Cannonball Kids’ Cancer Foundation to Munn will help hire a second nurse, an experienced pediatric nurse practitioner who previously worked at the children’s hospital. Johnson was also able to present preliminary data at the American Society of Pediatric Hematology/Oncology that was “well-received,” he said. “We’re starting to get some visibility on the national stage. We’re beginning to make an impact on the field.”

That wasn’t the case almost two years ago when Coulter was running out of options, said his mother, Courtney. He receives surgery at St. Jude Children’s Research Hospital and radiation therapy at M.D. Anderson Cancer Center and the radiation oncologist there urged the family to seek out a clinical trial that combined radiation with immunotherapy. Luckily for them, the clinical trial in Augusta was to open the next week.

“We flew out here on our way over to St. Jude’s for a brain surgery and then came back here right after that brain surgery,” Courtney Hnatt said. “Eighteen months later we’re still here, thankfully we’re still here. It’s a wonderful community.”

Johnson said they usually have long talks with families before they pick up and move to Augusta and he stresses to them that the therapy is not “curative.” Because it is a phase 1 clinical trial it cannot be compared in terms of effectiveness to other treatments.

“But what I can tell you is it is well-tolerated, it has not been toxic, the kids are on average having improvements in their quality of life,” he said. “At this late stage of treatments that is rather unusual.”

The parents have a less cautious assessment.

“At one point I thought she wasn’t going to make it,” Letitia Johnson said, looking at Jazzmyn as she huddled under a blanket in the clinic. “I’ve seen a big difference. It’s giving me hope. We’re not giving up.”

There is no quit in Coulter or his family as well.

“He’s doing really good, by the grace of God,” Courtney Hnatt said. “Recently he’s had some stable MRIs and he is handling the treatments well and he’s got great quality of life. We’re happy, we’re very pleased. It shows a lot of promise.”

 

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com

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