March 31, 2022

6 min read


Healio Interviews

Agrawal reports no relevant financial disclosures. Curran reports research funding from or a consultant/advisory board role with Celegene, Cellectis and Novartis.

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The FDA’s approval of tisagenlecleucel in 2017 resulted in an explosion of research into chimeric antigen receptor T-cell therapies.

However, much of this research has focused on adults.

Available pediatric CAR-T trials by state.

Data derived from information available at clinicaltrials.gov.

Data from clincialtrials.gov show more than 200 early phase or phase 1 clinical trials of CAR T-cell therapies are enrolling patients in the United States; however, fewer than 40 of these trials accept patients aged younger than 18 years. In addition, the CAR-T trials open to these younger patients are located in only 17 states and the District of Columbia.

There is an inherent inequity in access to early CAR-T trials, according to Anu K. Agrawal, MD, associate professor of clinical pediatrics at University of California, San Francisco, as well as hematologist-oncologist and bone marrow transplant specialist at UCSF Benioff Children’s Hospital Oakland.

First-in-human pediatric trials are conducted almost exclusively at a single center to start, forcing many study participants to travel great distances, Agrawal said. Potential referring physicians and younger patients’ caregivers also often are unaware of newly opened phase 1 trials.

Anu K. Agrawal, MD

Anu K. Agrawal

“It is hard to design an early phase 1 trial at more than one institution but, if we are trying to consider ways to achieve better access, we must first understand the problem and then try to design future early testing programs to address the issue,” Agrawal told Healio.

Healio spoke with two pediatric oncology specialists about the factors that limit timely enrollment of younger patients in pediatric CAR-T clinical trials, as well as the strategies the research and clinical communities have employed to try to expand access.

Increasing awareness

The primary challenge related to development of CAR T-cell therapies for younger patients is the lack of an easy-to-navigate system that provides essential information about available trials, Agrawal said.

“Going to a site like clinicaltrials.gov can be time-consuming, and it’s very difficult to search for potential trials,” he told Healio. “There is a lack of a unified information source that would provide families and referring providers information about what their patients may be eligible for.”

A single source of information that educates providers and their patients on the trial landscape — with updated trial status and contact information — would help enroll more younger patients, particularly for early-phase studies, Agrawal said.

Kevin J. Curran, MD, director of the Immune Effector Cell Program at Memorial Sloan Kettering Cancer Center and physician on the MSK Kids transplant and cellular therapy team, knows the precise search terms to use and centers to look for on clinicaltrials.gov that allow him to match a patient with an available study, but he understands he likely is the exception.

“I don’t know how useful clinicaltrials.gov would be to the average family member or community-level physician,” he told Healio.

Curran agreed a lack of information about available early-phase pediatric studies slows the pace of research due to slow enrollment.

“Raising awareness is necessary when you open a CAR T-cell [therapy] trial,” he said.

Nearly half of patients seeking early phase trial enrollment are self-referred. This means many community-level physicians who could refer patients often are unaware of what may be available.

Enrolling younger patients in new trials also has become more difficult because tisagenlecleucel (Kymriah, Novartis) is commercially available as a standard treatment for relapsed or refractory B-cell ALL. The number of patients seeking investigational therapies through trials decreased, Curran said.

Memorial Sloan Kettering is opening a new CAR-T trial for younger patients with acute myeloid leukemia. Curran said he will need to take steps to educate his colleagues about its existence.

Kevin J. Curran, MD

Kevin J. Curran

“The earlier physicians refer patients to a center like ours for a trial, the better, because we know patients do better when they are seen and treated earlier in their disease course,” he said. “Patients may miss their opportunity to participate in these trials unless there is awareness on the part of the patients or their referring physicians.”

Limited availability

The number of CAR-T trials for adults, as well as the number of locations at which patients can participate, has increased considerably during the past few years.

However, far fewer centers offer CAR-T trials for pediatric patients.

The limited number of sites, as well as uneven geographic distribution, mean many patients in need of an investigational therapy through clinical trials face access barriers due to socioeconomic status or lack of mobility.

“There may be 140-plus sites nationwide that provide Kymriah to younger patients with B-cell [acute lymphoblastic leukemia], but CAR-T clinical trials for pediatric patients are limited to maybe a couple dozen sites nationwide,” Agrawal said.

Agrawal’s institution is part of the Consortium for Pediatric Cellular Immunotherapy, which aims to accelerate clinical trial development and establish a network of centers for the testing of cellular therapy products.

Agrawal runs a patient advocacy committee through the consortium that strives to ensure equitable access to cellular therapies.

“Anytime you have an expensive therapy available at a limited number of institutions, you worry about inequitable access, whether it’s in terms of who can get to the site or who has knowledge of the trial,” he told Healio.

A consortium-led retrospective study revealed younger Hispanic or Latino patients face multiple barriers that limit timely access to CAR T-cell trials for relapsed or refractory B-cell ALL.

The results, presented at last year’s ASH Annual Meeting, showed that younger patients referred to urban academic centers for CAR-T clinical trials more often were non-Hispanic/Latino white. They also more often spoke English, had private insurance and typically traveled 40 times farther than locally referred patients.

Results showed Spanish-speaking patients and patients with public insurance were underrepresented in referrals from outside institutions, suggesting that language and socioeconomic status served as barriers to trial participation.

These factors have an impact on certain patients’ abilities to travel to a CAR-T trial site, Agrawal said.

“There is an incredible resource burden with having to travel for an extended period of time, and CAR-T trials involve multiple trips,” he said. “It’s not surprising that patients with access to more resources will be the ones more often gaining access to these trials.”

The onus typically is on a younger patient’s parents/caregiver or referring physician to express interest in participating in a CAR-T trial, Curran said. He agreed patients from lower socioeconomic backgrounds are underrepresented in clinical trial populations.

“There are families who have greater resources and are savvier at navigating the information about what is available,” Curran told Healio. “There is a real need for resources that allow patients to connect with providers.”

Addressing the problem

Regardless of the challenges facing clinical testing of novel CAR-T for younger patients, resources and strategies are available to accelerate the pace of progress.

Agrawal and UCSF received an infrastructure grant from St. Baldrick’s Foundation, which allotted more than $1 million to fund a clinical research associate at each of 24 institutions to help connect more younger patients to available clinical trials.

UCSF Benioff Children’s Hospital Oakland — which has received the grant for several years — uses the funding for a clinical research associate in its early-phase and cellular immunotherapy programs, and this helps ensure more children are treated in CAR-T trials.

The patient population Agrawal sees is highly diverse and skews toward lower socioeconomic status, with approximately 75% to 80% of patients having public insurance or no insurance.

“The funding St. Baldrick’s gave us has been vital … to not only getting [our early-phase trial program] started but allowing it to grow, as well,” Agrawal said.

Those who work in the cell therapy space would love to see additional products become available for both adults and children, Curran said. However, because of the limitations placed on early-phase trials for younger patients and the emphasis on safety, the fastest way to bring more cellular therapies to market for pediatric indications is to develop safer, more tolerable products for evaluation during early-phase trials.

Improving ease of use for CAR-T via less toxic therapies should be the goal, Curran said. Additionally, real-world studies of tisagenlecleucel for younger patients with B-cell ALL have shown lower rates of treatment-related toxicity than the pivotal clinical trials that led to approval, Curran said.

“The aim should be to move from B-cell ALL to AML, then to lymphoma and one day solid tumors,” he said. “Tisagenlecleucel was proof of principle that a CAR-T can be safe and effective for children, and now this must be built upon.”

For Curran, the most effective way to increase access to CAR-T trials for younger patients is safer therapies that can be administered in an outpatient setting. This would reduce the resource burden associated with trial participation and potentially expand the number of sites where investigational therapies can be offered.

“I firmly believe you don’t need to go to the ICU for these therapies to work,” Curran said.


Hall AG, et al. Abstract 339. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
St. Baldrick’s Foundation awards 24 infrastructure grants to help institutions bring lifesaving clinical trials closer to home (press release). www.stbaldricks.org/press-releases/st-baldricks-foundation-awards-24-infrastructure-grants-to-help-institutions-bring-lifesaving-clinical-trials-closer-to-home. Published Nov. 16, 2021. Accessed March 30, 2022.

For more information:

Anu K. Agrawal, MD, can be reached at UCSF Benioff Children’s Hospital Oakland, 747 52nd St., Oakland, CA 94609; email: [email protected].

Kevin J. Curran, MD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: [email protected].


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