Lentivirally Redirected CD123 Autologous T Cells in AML

NCT03766126 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 831619 (UPCC 35418)
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy 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 Acute Myeloid Leukemia (AML) subjects.

Conditions

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

Keywords

refractory; relapsed; Acute; Myeloid; leukemia; AML

Outcome Measures

Primary Outcomes (2)

• Safety profile of CART123 cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute (NCI) - Common Toxicity Criteria (v5.0)

  Assess the safety of CART123 cells in AML subjects following lymphodepletion with cyclophosphamide + fludarabine.

  5 years

• Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.

  Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.

  5 year

Secondary Outcomes (5)

• Estimation of CART123 efficacy by evaluation of OS and PFS of subjects at protocol defined intervals which receive at least one infusion of CART123 cells

  15 years

• Overall Survival (OS) as percent of subjects surviving at protocol defined time points.

  15 years

• Progression-free survival (PFS) as percent of subjects surviving without disease progression at protocol defined time points

  15 years

• Duration of response (DOR)

  15 years

• Necessity of rescue bone marrow transplant

  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 patients with relapsed/refractory AML. Subjects will be treated with a split dosing approach of CART123 cells (10% Day 0; 30% Day 1; 60% Day 2) for Cohort 1a/1b or a single IV administration of CART123 cells for Cohort 2. The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose, preceded by lymphodepleting chemotherapy, is 1-2x10\^6 CART123 cells/kg for Cohort 1a, 5x10\^6 CART123 cells/kg for Cohort 1b, or 2x10\^6 CART-123 cells/kg for Cohort 2. The protocol-specified minimum acceptable dose for infusion is 1x10\^5 CART123 cells/kg.

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

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects 18 years of age or older
• Subjects with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. Specifically:
• AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria (Döhner et al., 2017 Blood, 129(4):424-447); partial remission or refractory disease (including primary refractory) are eligible. Or:
• AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible
• Subjects with relapsed disease after prior transplant must meet one of the following:
• Subjects must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
• Satisfactory organ functions:
• Creatinine ≤ 1.6 mg/dl
• ALT/AST must be ≤5 x upper limit of normal unless related to disease
• Direct bilirubin or total bilirubin \< 2.0mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL);
• Left ventricular ejection fraction ≥ 40% as confirmed by ECHO/MUGA
• ECOG Performance status 0-2.
• Written informed consent is given.
• No contraindications for leukapheresis.
• Subjects of reproductive potential must agree to use acceptable birth control methods (as described in protocol Section 4.3).

You may not qualify if:

• Pregnant or lactating (nursing women) women.
• Patients with relapsed AML with t(15:17).
• HIV infection.
• Active hepatitis B or hepatitis C infection.
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 3).
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
• Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the Screening/Enrollment visit.
• Patients with any prior history of myeloproliferative neoplasm.
• Patients with the JAK2 V617F mutation by PCR or next generation sequencing.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Bhagwat AS, Torres L, Shestova O, Shestov M, Mellors PW, Fisher HR, Farooki SN, Frost BF, Loken MR, Gaymon AL, Frazee D, Rogal W, Frey N, Hexner EO, Luger SM, Loren AW, Martin ME, McCurdy SR, Perl AE, Stadtmauer EA, Brogdon JL, Fraietta JA, Hwang WT, Siegel DL, Plesa G, Aplenc R, Porter DL, June CH, Gill SI. Cytokine-mediated CAR T therapy resistance in AML. Nat Med. 2024 Dec;30(12):3697-3708. doi: 10.1038/s41591-024-03271-5. Epub 2024 Sep 27.

  PMID: 39333315 DERIVED

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: December 3, 2018
• First Posted: December 6, 2018
• Study Start: December 6, 2018
• Primary Completion (Estimated): December 3, 2033
• Study Completion (Estimated): December 3, 2033
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)