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

NCT07464951 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25CT017, 25-024116
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

CART; AML; CART123; Leukemia; Ruxolitinib

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Determine Feasibility of CART123 Treatment

  5 years

• Determine feasibility of combination treatment with CART123 and ruxolitinib

  5 years

• Determine the Preliminary Efficacy of CART123

  5 years

• Determine the Preliminary Efficacy of CART123 + Ruxolitinib

  5 years

• Evaluate the need for rescue stem cell transplant following treatment with CART123 or CART123 with Ruxolitinib

  5 years

Study Arms (2)

Cohort A

EXPERIMENTAL

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)

Cohort B

EXPERIMENTAL

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); Drug: Ruxolitinib (JAKAVI®)

Interventions

Ruxolitinib (JAKAVI®) DRUG

Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.

Cohort B

Anti-CD123 LV redirected T cells (CART123) BIOLOGICAL

CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.

Cohort A; Cohort B

Eligibility Criteria

• Age: 0 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. 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)
• \. Subjects with AML in second or greater relapse, post-transplant relapse, or with chemotherapy-refractory disease. Specifically:
• Second or greater relapse defined as bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy after second documented complete remission; OR
• Any detectable disease post-allogeneic transplant with bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy; OR
• Refractory disease, defined as: Persistent bone marrow involvement with ≥0.1% disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after two courses of induction chemotherapy for patients at initial presentation, ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of induction chemotherapy for patients who have relapsed after previously achieving a CR , and ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of AML-directed chemotherapy for those with myeloid lineage switch.
• \. Subjects must have an identified stem cell donor with the ability to proceed rapidly to transplant following CART123 treatment if indicated.
• \. Adequate organ function defined as:
• Serum creatinine based on age/gender.
• 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.
• 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.
• Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or another scan.
• \. Adequate performance status defined as Lansky or Karnofsky performance score ≥ 50.
• \. Subjects of reproductive potential must agree to use acceptable birth control methods.

You may not qualify if:

• \. Active hepatitis B or active hepatitis C
• \. HIV infection
• \. Active acute or chronic GVHD requiring systemic therapy
• \. 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.
• \. CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• \. Pregnant or nursing (lactating) subjects.
• \. Uncontrolled active infection

Sponsors & Collaborators

• Stephan Grupp MD PhD: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Lucy Cain, MBBS

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Stephan Grupp, MD, PhD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

Central Study Contacts

Cell Therapy Nurse Navigator

CONTACT

445-942-5891; CARTNurseNavigator@chop.edu

Melissa Varghese

CONTACT

varghesem@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 11, 2026
• Study Start: May 14, 2026
• Primary Completion (Estimated): May 14, 2029
• Study Completion (Estimated): May 14, 2030
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)