CD123 Redirected T Cells for AML in Pediatric Subjects

NCT04678336 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 834675 (19CT011)
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 open-label study to evaluate the safety of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia, Pediatric; Acute Myeloid Leukemia, Refractory

Keywords

refractory; relapsed; Acute; Myeloid; leukemia; AML

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of CART123 in AML subjects

  * Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells * Occurrence of dose-limiting toxicities (DLTs) and determination of Maximum Tolerated Dose (MTD)

  5 Years

Secondary Outcomes (4)

• Evaluate study feasibility

  15 Years

• Evaluate manufacturing feasibility

  15 Years

• Describe preliminary efficacy

  15 Years

• Evaluate the need for rescue alloHCT

  15 Years

Other Outcomes (2)

• Determine persistence and trafficking of CART123 cells

  15 Years

• Analyze CART123 bioactivity

  15 Years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

CART123 cells; cyclophosphamide; fludarabine

Biological: CART123 cells; cyclophosphamide; fludarabine

Interventions

CART123 cells; cyclophosphamide; fludarabine BIOLOGICAL

CART123 cells following lymphodepleting chemotherapy in pediatric patients with relapsed/refractory AML. Subjects will be treated with a single IV dose of CART123 cells on Day 0.

Also known as: T Cells Containing Anti-CD123 Signaling Domains

Treatment Arm

Eligibility Criteria

• Age: 1 Year - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male and female patients ≥ 1 and ≤ 29 years of age at time of consent.
• AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically:
• Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR
• Any detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1% (as confirmed by Hematologics); OR
• Refractory disease, defined as persistent bone marrow involvement with \>5% blasts after two courses of induction chemotherapy for patients at initial presentation or \>5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR.
• Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion.
• Adequate organ function defined as:
• A serum creatinine based on age/gender
• Adequate liver function
• i. ALT ≤ 5 x ULN
• ii. Total bilirubin ≤ 3 x ULN
• iii. 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.
• c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \< Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
• d. Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
• Adequate performance status defined as Lansky or Karnofsky score ≥ 50

You may not qualify if:

• Pregnant or lactating (nursing) women.
• Patients with relapsed AML with t(15:17).
• Patients \< 6 months from alloHSCT.
• HIV infection.
• Active hepatitis B or hepatitis C infection.
• Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
• Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroids and immunosuppressant medications (including washout requirements prior to CAR T cell administration).
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• Uncontrolled active infection
• Subjects with CNS3 disease that is progressive on therapy or with CNS parenchymal lesions that may increase the risk of CNS toxicity. Subjects with adequately treated CNS leukemia are eligible.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Patients with any prior history of myeloproliferative neoplasm.
• Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Leukemia

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: December 21, 2020
• Study Start: April 2, 2021
• Primary Completion: May 9, 2025
• Study Completion: May 9, 2025
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)