CART123 Cells With or Without Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia (CART123)

Phase 1 Trial of Autologous CD123-Directed CAR T-Cells (CART123) as Monotherapy or in Combination With Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia

This study is designed to evaluate the safety and effectiveness of CART123 cells either alone or when combined with ruxolitinib in pediatric and young adult subjects with relapsed or refractory AML. Subjects will be enrolled into one of two treatment cohorts: subjects who will receive CART123 alone (Cohort A) or subjects who will receive CART123 in combination with ruxolitinib (Cohort B).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Biological: Anti-CD123 LV redirected T cells (CART123); Drug: Ruxolitinib (JAKAVI®)

Detailed Description

This trial will be conducted at the Children's Hospital of Philadelphia with CART123 infusions occurring in an outpatient setting with close follow-up. Approximately 18 subjects will be treated on Cohort A and 12 patients treated on Cohort B.

Cohort A will consist of a dose escalation of CART123 cells administered intravenously on Day 0 after lymphodepleting chemotherapy. Subjects enrolled on Cohort A will receive a standard regimen of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (500 mg/m2/day x 2 days). There is the most experience with the use of this regimen in facilitating adoptive immunotherapy in completed and ongoing pediatric CART trials.

Cohort B will consist of a fixed dose of CART123 cells (2x10^6 CART123 cells/kg) to be administered intravenously on Day 0 in combination with age and BSA-based dosing of ruxolitinib given orally from the start of lymphodepleting chemotherapy until Day -2 and again from Day+7 to Day+13. Subjects enrolled on Cohort B will receive the regimen fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (1000 mg/m2/day x 3 days). This regimen of enhanced lymphodepletion has been employed with other investigational CAR T-cell therapies with the goal of improving CAR T-cell expansion. There is no dose escalation of CART123 cells or ruxolitinib on this cohort, but a dose de-escalation of ruxolitinib is planned in the event of unacceptable toxicity defined by dose de-escalation rules.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cell Therapy Nurse Navigator; Phone Number: 445-942-5891; Email: CARTNurseNavigator@chop.edu
• Study Contact Backup: Name: Melissa Varghese; Email: varghesem@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: CART Nurse Navigator; Phone Number: 445-942-5891; Email: cartnursenavigator@chop.edu
      • Contact: Melissa Varghese, MS; Email: varghesem@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age at time of consent: Cohort A: 0-29 years. Cohort B: 1-29 years (Note: the first subject at each dose level of Cohort B must be ≥12 years old)

• 2. Subjects with AML in second or greater relapse, post-transplant relapse, or with chemotherapy-refractory disease. Specifically:

  1. Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR
  2. Any detectable disease post-allogeneic transplant with flow cytometric confirmation of myeloid leukemia of at least 0.1%; OR
  3. Refractory disease, defined as: Persistent bone marrow involvement with >5% blasts after two courses of induction chemotherapy for patients at initial presentation, >5% bone marrow blasts after one course of induction chemotherapy for patients who have relapsed after previously achieving a CR, and >5% bone marrow blasts after one course of AML-directed chemotherapy for those with myeloid lineage switch.
• 3. Subjects must have an identified stem cell donor with the ability to proceed rapidly to transplant following CART123 treatment if indicated.

• 4. Adequate organ function defined as:

  1. Serum creatinine based on age/gender.
  2. Adequate liver function: ALT ≤ 500 U/L, Bilirubin ≤3x the upper limit of normal, and ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to AML infiltration of the liver.
  3. Must have a minimum level of pulmonary reserve defined as ≤Grade 1 dyspnea and <Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the treating investigator.
  4. Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or another scan.
• 5. Adequate performance status defined as Lansky or Karnofsky performance score ≥ 50.
• 6. Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria:

• 1. Active hepatitis B or active hepatitis C
• 2. HIV infection
• 3. Active acute or chronic GVHD requiring systemic therapy
• 4. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
• 5. CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• 6. Pregnant or nursing (lactating) subjects.
• 7. Uncontrolled active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; In Cohort A, the treatment regimen will consist of lymphodepleting chemotherapy followed by CART123 infusion with planned dose escalation. Subjects enrolled on Cohort A will receive a standard regimen of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (500 mg/m2/day x 2 days).	Biological: Anti-CD123 LV redirected T cells (CART123); CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.
Experimental: Cohort B; In Cohort B, the treatment regimen will consist of lymphodepleting chemotherapy and ruxolitinib followed by a fixed dose of CART123 cells and age and body surface area-adjusted dose of ruxolitinib. Subjects enrolled on Cohort B will receive the regimen fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (1000 mg/m2/day x 3 days).	Biological: Anti-CD123 LV redirected T cells (CART123); CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.; Drug: Ruxolitinib (JAKAVI®); Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Safety of CART123	Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123	5 years
Safety of CART123 in combination with Ruxolitinib	Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123 and Ruxolitinib	5 Years
Determine Maximum Tolerated Dose of CART123	The Maximum Tolerated Dose will be determined by measuring the incidence of dose limiting toxicities following administration of the CART123 product.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Feasibility of CART123 Treatment	Measured by the proportion of enrolled subjects who receive CART123 infusion.	5 years
Determine feasibility of combination treatment with CART123 and ruxolitinib	Measured by the rate of enrolled subjects who receive CART123 infusion and at least 7 days of ruxolitinib.	5 years
Determine the Preliminary Efficacy of CART123	Measured by the rate of subjects who achieve complete remission following treatment with CART123 at Day 28.	5 years
Determine the Preliminary Efficacy of CART123 + Ruxolitinib	Measured by the rate of subjects who achieve complete remission following treatment with CART123 and at least 7 days of Ruxolitinib at Day 28.	5 years
Evaluate the need for rescue stem cell transplant following treatment with CART123 or CART123 with Ruxolitinib	Determine the proportion of infused subjects who proceed to allogeneic HSCT for bone marrow aplasia following treatment with CART123 or CART123 with Ruxolitinib	5 years

Collaborators and Investigators

• Sponsor: Stephan Grupp MD PhD
• Collaborators: Children's Hospital of Philadelphia
• Investigators: Study Director: Stephan Grupp, MD, PhD, Children's Hospital of Philadelphia; Principal Investigator: Lucy Cain, MBBS, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2026
• Primary Completion (Estimated): May 14, 2029
• Study Completion (Estimated): May 14, 2030

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 7, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ruxolitinib; AML; Leukemia; CART; CART123
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid, Acute; ruxolitinib
• Other Study ID Numbers: 25CT017, 25-024116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No