Acute Myeloid Leukemia (AML)Phase 1CART123NCT07464951
CART123 Cells With or Without Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing Anti-CD123 LV redirected T cells (CART123) and Ruxolitinib (JAKAVI®) in people with Acute Myeloid Leukemia (AML), run by Stephan Grupp MD PhD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 29 years
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Anti-CD123 LV redirected T cells (CART123) and Ruxolitinib (JAKAVI®)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2026to 14 May 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
- 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.
- 3. Subjects must have an identified stem cell donor with the ability to proceed rapidly to transplant following CART123 treatment if indicated.
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- 4. 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.
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Melissa Varghese contact
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
CART Nurse Navigator, 445-942-5891, cartnursenavigator@chop.edu
Melissa Varghese, MS, varghesem@chop.edu
About this study
Official title: 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).
Read the 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.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Anti-CD123 LV redirected T cells (CART123), Ruxolitinib (JAKAVI®)
- Keywords
- CART, AML, CART123, Leukemia, Ruxolitinib
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Ruxolitinib (JAKAVI®)Drug
Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Biological: Anti-CD123 LV redirected T cells (CART123); Drug: Ruxolitinib (JAKAVI®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 5 years
Secondary outcomes (5)
Determine Feasibility of CART123 Treatment
Measured by the proportion of enrolled subjects who receive CART123 infusion.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start14 May 2026
- Primary completion14 May 2029 (estimated)
- Study completion14 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stephan Grupp MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Sponsor-investigator, Stephan Grupp MD PhD, Children's Hospital of Philadelphia
- Investigators
- Lucy Cain, MBBS, Principal investigator, Children's Hospital of PhiladelphiaStephan Grupp, MD, PhD, Study director, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07464951
- Sponsor's protocol ID
- 25CT017, 25-024116
- Acronym
- CART123
- Status last verified
- Jul 2026
- First submitted
- 4 Mar 2026
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No