CART123 Cells + Ruxolitinib for AML

(CART123 Trial)

CT
MV
Overseen ByMelissa Varghese
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with acute myeloid leukemia (AML) that hasn't responded to other treatments or has recurred. It examines the safety and effectiveness of a special cell therapy called CART123, used alone or with another medication, ruxolitinib (a JAK inhibitor). The trial divides participants into two groups: one receives only CART123, while the other receives CART123 with ruxolitinib. Ideal participants are young individuals who have experienced multiple AML relapses or haven't responded to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications. However, you cannot use systemic steroids or immunosuppressants at the time of cell infusion or collection, unless they are for disease treatment at other times. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, CART123 cells showed promise in treating relapsed or hard-to-treat acute myeloid leukemia (AML). Research suggests these cells can locate and destroy leukemia cells. However, some patients experienced side effects, though the specifics are not always clear.

Regarding ruxolitinib, studies have found it generally well-tolerated by AML patients. Most people did not experience severe side effects, with only a few facing more serious health issues. Ruxolitinib has been safely used with other AML treatments, indicating it can be a reliable part of a treatment plan.

Both treatments have demonstrated potential in earlier research, but the combination of CART123 cells and ruxolitinib is still under study for safety and effectiveness. Researchers will closely monitor trial participants to ensure their well-being.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about CART123 cells combined with ruxolitinib for treating acute myeloid leukemia (AML) because of their unique approach. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, CART123 cells are designed to specifically target and destroy cancer cells expressing the CD123 protein. This precision could potentially reduce collateral damage to healthy cells. In Cohort A, CART123 cells are used after chemotherapy with dose escalation, offering a tailored response. Meanwhile, in Cohort B, the addition of ruxolitinib, a JAK inhibitor, aims to enhance the anti-cancer effects by modulating the immune environment, showing promise in improving outcomes for patients with AML.

What evidence suggests that this trial's treatments could be effective for AML?

Studies have shown that CART123 cells can help about 25% of adults with relapsed or hard-to-treat acute myeloid leukemia (AML) respond positively to treatment. These cells are specially designed to find and destroy cancer cells with a marker called CD123. In this trial, participants in Cohort A will receive CART123 cells following lymphodepleting chemotherapy. Meanwhile, Cohort B will receive a combination of CART123 cells and ruxolitinib, which treats certain blood disorders, following lymphodepleting chemotherapy. Research suggests that this combination might enhance the effectiveness of CART123 by overcoming resistance in AML. These treatments are under study because they could significantly improve the survival and recovery of patients with challenging cases of AML.12345

Who Is on the Research Team?

LC

Lucy Cain, MBBS

Principal Investigator

Children's Hospital of Philadelphia

SG

Stephan Grupp, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children and young adults (up to 29 years old) with acute myeloid leukemia that has come back or not responded to treatment. Participants need good organ function, a stem cell donor available, and must not be pregnant, breastfeeding, have active infections like hepatitis or HIV, or require ongoing steroids.

Inclusion Criteria

I have a stem cell donor ready if I need a transplant after CART123 treatment.
I am between 0 and 29 years old.
My AML has come back at least twice, after transplant, or did not respond to chemo.
See 1 more

Exclusion Criteria

I am not taking steroids or immunosuppressive drugs now or expected to need them soon.
Pregnant or nursing (lactating) subjects
I currently have active hepatitis B or C.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CART123 infusion

1 week
1 visit (in-person)

Treatment

Cohort A: Dose escalation of CART123 cells; Cohort B: Fixed dose of CART123 cells with ruxolitinib

1 day for infusion, 7 days for ruxolitinib
Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • CART123 Cells
  • Ruxolitinib

Trial Overview

The study tests CART123 cells (a type of modified immune cell therapy) alone versus in combination with ruxolitinib. Participants are randomly assigned to one of the two groups to see which approach is safer and more effective for relapsed/refractory AML.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Group I: Cohort BExperimental Treatment2 Interventions
Group II: Cohort AExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Stephan Grupp MD PhD

Lead Sponsor

Trials
5
Recruited
370+

Children's Hospital of Philadelphia

Collaborator

Trials
749
Recruited
11,400,000+

Citations

CD123-directed chimeric antigen receptor T-cell (CART123 ...

Investigation of an autologous 4-1BB CD123-directed CAR (CART123) in adults with r/r AML yielded responses in 25% (PMID 39333315). We now report ...

CD123-directed chimeric antigen receptor T-cell ...

Investigation of an autologous 4-1BB CD123-directed CAR (CART123) in adults with r/r AML yielded responses in 25% (PMID 39333315). We now report ...

CYTOKINE-MEDIATED CAR T THERAPY RESISTANCE IN AML

Here we report a pilot study of autologous anti-CD123 CAR T cells in 12 adults with relapsed or refractory AML. CART cells targeting CD123+ cells were ...

Transduced T Cells (CART123) for the Treatment of ...

These changed cells are called CART123 cells. Giving CART123 cells may kill more tumor cells in patients with relapsed or refractory acute myeloid leukemia.

NCT04014881 | Safety and Efficacy of Anti-CD123 CAR-T ...

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ ...