Research and Clinical Trials
T-Cell Immunotherapy for Leukemia and Lymphoma (PLAT)
Seattle Children’s doctors and researchers are leading efforts to better treat leukemia and lymphoma in children and young adults by boosting the immune system.
T-cell immunotherapy is an experimental new cancer treatment that stimulates the immune system to fight disease. It is a type of targeted therapy (also known as biotherapy).
Food and Drug Administration–authorized trials at Seattle Children’s are testing T-cell therapy in children and young adults with relapsed or refractory acute leukemia or lymphoma who are not likely to survive with current treatments.
Several of these trials are known as Pediatric Leukemia Adoptive Therapy (PLAT). These trials are testing chimeric antigen receptor (CAR) T-cell immunotherapy.
Doctors hope that when T-cell therapy is fully tested:
- It will work quickly, so treatment takes weeks, not years.
- It will have milder side effects than other treatments, like chemotherapy.
What is the goal of the PLAT studies?
PLAT includes phase 1 and phase 2 trials. Phase 1 trials focus on finding out how much of a therapy to give, how to give it, how often to give it and when side effects occur. Phase 2 trials look at whether a therapy is safe and whether it works in people who have a certain disease.
Through the PLAT studies, researchers are working to answer these questions:
- Is T-cell therapy safe to give to children and young adults with relapsed or refractory acute leukemia or lymphoma?
- What is the largest dose that children and young adults can stand (the maximum tolerated dose)?
- Does T-cell therapy work against leukemia and lymphoma?
In PLAT-02, the CAR T cells are reprogrammed to recognize and target the CD19 protein expressed by most leukemia and lymphoma cells.
The first phase of PLAT-02 was important in establishing the safety of this experimental therapy, short-term side effects and the maximum dose of T cells.
Phase 2 began in June 2016 and met its enrollment goal for patients with leukemia in late 2019. It is currently enrolling patients with relapsed or refractory lymphoma.
PLAT-03 is a pilot study that will test the feasibility and safety of giving a series of 1 to 6 “booster” infusions called T-cell antigen-presenting cells (T-APCs). These will be given to children and young adults after they receive their initial CAR T-cell therapy. The infusions of T-APCs are intended to make the patient’s reprogrammed cancer-fighting T cells last longer.
PLAT-03 is now open to patients who:
- Have relapsed or refractory CD19+ leukemia
- Are also identified as being at risk for losing their reprogrammed T cells shortly after T-cell therapy
- After receiving T cells through PLAT-02 have lost their reprogrammed T cells within 6 months
PLAT-03 opened for enrollment in May 2017 and is currently recruiting.
PLAT-04 is a phase 1 trial that tests the safety and feasibility of CAR T cells that have been reprogrammed to target the CD22 protein expressed by some leukemia cells.
The PLAT-02 trial uses CAR T cells that have been reprogrammed to target the CD19 protein. However, in some patients, the leukemia comes back (recurs) and has evolved so it doesn’t express CD19 anymore, but it continues to express another protein, CD22.
Our researchers developed PLAT-04 as an investigational treatment option that will hopefully lead to long-term remission for patients whose cancer expresses CD22.
PLAT-04 is currently closed to new patients but will likely reopen in 2020 for additional enrollments.
PLAT-05 is a first-in-the-nation pediatric phase 1 trial that tests the safety and feasibility of CAR T cells that have been reprogrammed to target CD19 and CD22 proteins simultaneously. CD19 and CD22 are expressed by most leukemia cells.
Our researchers developed PLAT-05 as an investigational treatment option that will hopefully lead to long-term remission for patients whose cancer expresses CD19 and CD22.
PLAT-05 opened for enrollment in November 2017 and is currently recruiting.
Is T-cell therapy effective?
The clinical trials needed to answer that question are ongoing, but early results are very promising.
In April 2017, Seattle Children's published in Blood that 40 of 43 patients treated in the phase 1 PLAT-02 clinical trial achieved complete initial remission.
- This 93% remission rate was confirmed by highly sensitive tests designed to detect tiny amounts of cancer cells.
- The 40 patients who have achieved complete remission included children with very high tumor burdens, as well as children who were diagnosed with acute lymphoblastic leukemia (ALL) as infants. When they started the clinical trial, patients had less than a 20% chance of survival using current treatments.
- Of the patients who achieved initial remission, about 50% are still in remission 1 year after therapy. Some are still in remission more than 5 years after therapy. For the patients whose cancer came back, researchers have found that either their reprogrammed T cells are no longer in their body or the cancer cells have changed so that the T cells cannot find and destroy them.
Relapse is a challenge in CAR T-cell trials across the country. Seattle Children’s researchers are dedicated to improving the therapy with the goal of long-term remission for all patients and – ultimately – a cure. Based on what they’ve learned from previous trials, our research team developed new PLAT trials and is now testing innovative ways to cut the relapse rate (PLAT-03, -04, and -05).
After patients receive an infusion of their reprogrammed T cells, some can experience a side effect called cytokine release syndrome (CRS). This usually involves a fever and changes in blood pressure. Other patients can experience neurological side effects that typically involve temporary confusion or being overly tired (lethargy). In rare cases, these side effects could be more severe.
Who can join the PLAT studies?
The PLAT studies are for children and young adults who:
- Have relapsed or refractory pre-B acute lymphoblastic leukemia (ALL) or other CD19+ or CD22+ acute leukemia or CD19+ lymphoma. It is not open to young people with other leukemias or other childhood cancers.
- Are ages 1 to 26 years old.
- Researchers use many other factors to decide whether a patient can take part in a study (inclusion criteria) or cannot take part (exclusion criteria). The study team at Seattle Children’s can explain what these factors mean for you or your child.
Are there studies for other childhood cancers?
- AML, T-cell ALL and B-cell ALL: HA-1 is a phase 1 clinical trial testing a type of T-cell therapy for children and young adults with relapsed or refractory acute leukemia or leukemia that does not respond to treatment after a donor stem cell transplant.
- Brain and central nervous system tumors: BrainChild-01 and -02 are phase 1 clinical trials testing T-cell therapy in children and adolescents with recurrent or refractory brain or central nervous system (CNS) tumors that express the protein HER2 or EGFR.
- Neuroblastoma: ENCIT is a phase 1 clinical trial testing T-cell therapy in children and adolescents with recurrent or refractory neuroblastoma.
- Solid tumors: STRIvE-01 is a phase 1 clinical trial testing T-cell therapy in children and young adults with relapsed or refractory solid tumors that express the protein EGFR.
- See many of Seattle Children's open clinical trials on our Current Research Studies page.
- Or search by diagnosis for many clinical trials available through Seattle Children's and our partners on ClinicalTrials.gov. Read our guide about searching for trials on ClinicalTrials.gov (PDF).
Who is leading the trials?
- PLAT-02 and -05: Dr. Rebecca Gardner
- PLAT-03: Dr. Colleen Annesley
- PLAT-04 and HA-1: Dr. Corinne Summers
All are doctors in the Cancer and Blood Disorders Center at Seattle Children’s.
For more information, call 206-987-2106 or send us an email.
- Read about how CAR T-cell therapy works.
- Learn about our integrated High-Risk Leukemia Program.
- Read about how our program developed in “Fighting for Their Lives: Seattle Children’s Immunotherapy Journey.”
- Learn about Seattle Children's Immunotherapy Integration Hub.
Updated September 2019.