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Leukemia, Myeloid, Acute

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Myeloid Leukemia

Acute Myeloid Leukemia

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Cyclophosphamide

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Fludarabine phosphate

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Alkylating Agents

CART123 cells; cyclophosphamide; fludarabine

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)

University of Pennsylvania

Anti-Infective Agents

Analgesics

Etoposide

Cytarabine

Mitoxantrone

Daunorubicin

Etoposide phosphate

Homoharringtonine

Idarubicin

The induction course was Daunorubicin(DNR) + Cytarabine(Ara-C) or Homoharringtonine(HHT) + Ara-C or HHT + DNR + Ara-C. There are 5 consolidation course after complete remission (CR).

The induction course was MAE(Mitoxantrone + Cytarabine + Etoposide) or IAE(Idamycin + Cytarabine + Etoposide). Risk-stratified therapy and dose-dense intensive chemotherapy were adopted in the consolidation therapy. After the second course of therapy, patients in remission were stratified into three risk groups: low-risk children were defined as those with t(8;21) and a white blood cell count lower than 50,000/L, inv(16), or an age younger than 2 years without any high-risk factors; high-risk children were those with CR after consolidation course 1 or induction C , or with abnormalities of monosomy 7, 5q-, t(16;21), t(9;22)(Philadelphia chromosome \[Ph1\]); intermediate-risk children were those who were not in either a low-risk or high-risk group. Hematopoietic stem cell transplantation (HSCT) was indicated for only relapsed patients in the second CR.

Dose-dense intensive chemotherapy and high dose of Ara-C in the consolidation therapy.

Risk-stratified therapy

Zhu Xiaofan

The investigators adopted the CAMS（Chinese Academy of Medical Sciences）-2009 trial for pediatric acute myeloid leukemia (AML) patients between 2009 to 2015, in which a risk-stratified strategy and dose-dense intensive chemotherapy were introduced. The outcomes of CAMS-2009 trial were retrospectively analyzed, and compared to the CAMS-2005 trial.

Efficacy Analysis of Comparison of CAMS（Chinese Academy of Medical Sciences）-2005 Trial and CAMS-2009 Trial for Pediatric Acute Myeloid Leukemia

Efficacy Analysis of Comparison of CAMS-2005 Trial and CAMS-2009 Trial for Pediatric Acute Myeloid Leukemia

The outcomes of CAMS（Chinese Academy of Medical Sciences）-2009 trial are retrospectively analyzed, and compared to the CAMS-2005 trial.

fewer than 5% blast cells in the bone marrow aspirate and the absence of extramedullary involvement (EMI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Efficacy Analysis of Comparison of CAMS（Chinese Academy of Medical Sciences）-2005 Trial and CAMS-2009 Trial for Pediatric Acute Myeloid Leukemia	NCT03165851	Acute Myeloid L...	Risk-stratified...	6 Months - 16 Years	Institute of Hematology & Blood Diseases Hospital, China

Spots Global Cancer Trial Database for acute myeloid leukemia, pediatric