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CART123 cells; cyclophosphamide; fludarabine

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.

EmergingMed

Care Box Health

Saar Gill, MD, PhD

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.

This is a Phase 1 study to determine the safety, feasibility, and efficacy of 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 for all cohorts.

It is recommended per routine clinical care, that all subjects with marrow aplasia at Day 28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study, however subjects will continue to be followed on study. All subjects should therefore have a previously identified stem cell donor in order to participate in this study. Please see Section 6.8 for additional details.

All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion (Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.

Lentivirally Redirected CD123 Autologous T Cells in AML

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Refractory or Relapsed Acute Myeloid Leukemia

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

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

Estimate the efficacy of at least 1 dose of CART123 cells in AML subjects

Overall survival (OS) and progression-free survival (PFS)

Need for rescue allogeneic hematopoietic cell transplantation (alloHCT)

University of Pennsylvania

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.

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 pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).

This is a Phase 1 study to determine the safety, manufacturing feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in pediatric subjects with relapsed/refractory AML.

Subjects will receive CART123 cells via a single IV infusion at a dose of 2x10\^6 CART123 cells/kg, following lymphodepleting chemotherapy. The total dose administered to each subject will be based on the subject's body weight obtained at the time of apheresis. The minimum acceptable dose for infusion is 1x10\^5 CART123 cells/kg.

There will be a 28-day stagger between the first 3 subject infusions, such that the next subject may not receive treatment (lymphodepleting chemotherapy plus CART123 cells) until the previous subject has completed their Day 28 safety follow-up visit and a DLT assessment has been performed. Subsequent infusions will be staggered by a minimum of 14 days.

It is recommended that subjects with marrow aplasia at Day 28+/-5 undergo an allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study; however, subjects will continue to be followed onstudy. All subjects must, therefore, have a previously identified stem cell donor as part of their eligibility to participate in this study.

All subjects will be followed monthly for up to 6 months after the CART123 cell infusion (Day 0). Thereafter, subjects will be transitioned into LTFU for up to 15 years post infusion.

CD123 Redirected T Cells for AML in Pediatric Subjects

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Pediatric Subjects With Refractory or Relapsed Acute Myeloid Leukemia

The duration of in vivo survival of CART123 cells ("persistence") is defined as the period of time above the limit of detection of Q-PCR for peripheral blood CART123 transgene sequences and/or flow cytometry for scFv surface expression.

Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells

Percentage of manufacturing products that meet release criteria

Overall Response Rate (ORR) at 28 +/- 5 days

1. Standard morphologic complete response criteria (malignant blasts \< 5% with count recovery)
2. Malignant blasts \< 5% without count recovery, and
3. Minimal residual disease assessment

Change 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

Progression-free survival (PFS) for all subjects; PFS will be followed until the time of first relapse or receipt of additional therapy, excluding alloHCT for marrow aplasia.

Time between date of when the response criteria of CR/CRi was met to the date of relapse

Percentage of subjects proceeding to alloHCT (or second allogeneic HCT)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lentivirally Redirected CD123 Autologous T Cells in AML	NCT03766126	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	18 Years -	University of Pennsylvania
CD123 Redirected T Cells for AML in Pediatric Subjects	NCT04678336	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	1 Year - 29 Years	University of Pennsylvania
CD123 Redirected T Cells for AML in Pediatric Subjects	NCT04678336	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	1 Year - 29 Years	University of Pennsylvania

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