CART123 + Ruxolitinib in Relapsed/Refractory AML (AML)

Phase I Trial of CART123 Cells Given in Combination With Ruxolitinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Phase I, open-label study to assess the safety, feasibility, pharmacokinetics, and preliminary efficacy of CART123 cells given in combination with ruxolitinib in patients with relapsed or refractory acute myeloid leukemia (AML). All subjects will receive a single infusion of CART123 cells following ruxolitinib administration and lymphodepletion. Ruxolitinib dosing will begin at initiation of lymphodepleting chemotherapy (Day -6 ±1d) and continue for up to 14 days post CART123 administration.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed AML; Refractory AML
• Intervention / Treatment: Biological: CART123 Cells; Drug: Ruxolitinib 5 MG; Drug: Ruxolitinib 10 MG

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Signed informed consent form 2. Male or female age ≥ 18 years. 3. Patients with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. This is specifically defined as one of the following:

  1. AML that has not achieved a complete remission or morphologic leukemia free state by ELN 2022 criteria57 after at least 2 cycles of induction (includes partial remission or refractory/primary refractory disease), OR:
  2. AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplant).

  i. Note: Morphologic relapse is not required; Patient may have persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (i.e., MRD) at any time after allogeneic HCT to qualify. Mutations involving DNMT3A, ASXL1 or TET2 should not count as molecular MRD+ disease unless accompanied by other, more specific disease-related molecular or cytogenetic abnormalities.

  4. Patients with relapsed disease after prior allogeneic SCT must be at least 3 months from transplantation (where receipt of the stem cell product is defined as day 0) and must not require systemic immunosuppression (for prevention or treatment of GVHD).

  5. Patients must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion if clinically indicated. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria.

  6. Adequate organ function defined as:

  1. Estimated creatinine clearance > 35mL/min using the CKD-EPI equation for Glomerular Filtration Rate (GFR); Patients must not be on dialysis
  2. ALT/AST ≤ 5x upper limit of normal range
  3. Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl)
  4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air

  5. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by transthoracic echocardiography or MUGA scan.

     7. ECOG Performance Status 0-2.

     Exclusion Criteria:

• 1. Patients with the JAK2 V617F mutation by PCR or next generation sequencing. 2. Patients with signs or symptoms indicative of active CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.

  3. Patients with relapsed AML with t(15:17). 4. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.

  5. Active acute or chronic GVHD requiring systemic therapy. 6. Class III/IV cardiovascular disability according to the New York Heart Association Classification.

  7. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.

  8. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.

  9. Planned use of fluconazole within the anticipated study treatment window. For additional details on concomitant medication restrictions.

  10. Receipt of prior CART123 therapy. 11. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

  12. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

  13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: DL1; LD Chemo: Day -6 to Day -4 (±1d); Ruxolitinib: Daily beginning on Day -6 (±1d) through D14 post CART123 infusion.; CART123 Cells: Single infusion on Day 0	Biological: CART123 Cells; 1.3x10^8 CART123 cells; Drug: Ruxolitinib 10 MG; Twice Daily
Experimental: Arm A: DL-1; LD Chemo: Day -6 to Day -4 (±1d); Ruxolitinib: Daily beginning on Day -6 (±1d) through D14 post CART123 infusion.; CART123 Cells: Single infusion on Day 0	Biological: CART123 Cells; 1.3x10^8 CART123 cells; Drug: Ruxolitinib 5 MG; Twice Daily
Experimental: Arm B: DL-1; LD Chemo: Day -6 (-1d) to Day -2 (-1d); Venetoclax: Day -6 (-1d) through Day +7 - Day +14 post-CART123 infusion; Ruxolitinib: Daily beginning on Day -1 through Day +7 post CART123 infusion.; CART123 Cells: Single infusion on Day 0	Biological: CART123 Cells; 1.3x10^8 CART123 cells; Drug: Ruxolitinib 5 MG; Twice Daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety of CART123 cells when given in combination with ruxolitinib	Type, frequency, severity, and attribution of AEs/SAEs, including the incidence and severity of IEC-associated adverse events.	15 Years
Evaluate the safety of CART123 cells when given in combination with ruxolitinib	Occurrence of treatment-limiting toxicities (TLTs)	3 months
Evaluate the safety of CART123 cells when given in combination with ruxolitinib	The proportion of subjects requiring ruxolitinib dose modifications by assigned dose.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate study feasibility	The proportion of eligible subjects who receive both investigational products as per protocol.	3 months
Evaluate study feasibility	The proportion of eligible subjects who receive all planned doses of ruxolitinib.	3 months
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Objective Response Rate (ORR) at Day 28	From enrollment to Day 28, post treatment.
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Duration of Response (DOR)	15 years
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Progression-free survival (PFS)	15 Years
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Overall Survival (OS)	15 Years
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Reduction of blast count in the peripheral blood and marrow using standard clinical criteria (CBC with differential count, marrow aspirate with differential count) and flow cytometry at Day 28	From enrollment to Day 28, post treatment.
Describe preliminary efficacy of CART123 cells given in combination with ruxolitinib	Percentage of subjects undergoing alloHCT	15 Years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Novartis
• Investigators: Principal Investigator: Saar Gill, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): March 1, 2045
• Study Completion (Estimated): March 1, 2045

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: acute; AML; relapsed; refractory; leukemia; CART; myeloid
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia; Leukemia, Myeloid, Acute; ruxolitinib
• Other Study ID Numbers: 50424

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