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CAR T-cells for AML
Table 1. Chimeric antigen receptor (CAR) T-cell therapy trials for patients with acute myeloid leukemia open for enrollment.
Disease and key inclusion/ exclusion criteria
RR AML
- >18 yo
- alloHSCT eligible with stem cell source identified
- if relapsed post prior alloHSCT, must be off
immune suppression and have no active GvHD (>Gr II)
RR AML or relapsed BPDCN
- >12 yo
- alloHSCT eligible with stem cell source identified
- if relapsed post prior alloHSCT, must be off
immune suppression
RR AML or ELN adverse AML in up-front treatment
- 18-65 yo
- if relapsed post prior alloHSCT, must be off
immune suppression for 6 wks, and have no
evidence of GvHD
- CD123(+)blastsbystandardflow
cytometry
RR AML
- Pediatric 1-18yo
- Adult >18-80yo
- if relapsed post prior alloHSCT, must be
at least 3 mo post alloHSCT, be off immune
suppression, and have no evidence of GvHD
Relapsed AML after alloHSCT
- >18 yo
- CD123(+) by IHC and flow cytometry
- Original alloHSCT donor available
to donate fresh PBMC for CART manufacture (or sufficient cells are cryopreserved)
RR AML / MDS / MPN / CML or other hematologic malignancy
- Child / adult / older adult (ages not stated)
- if relapsed post prior alloHSCT, must be
at least 6 mo post alloHSCT, be off immune suppression at least 4 wks, and have no evidence of GvHD
RR AML
- <70years
RR AML
- 14 – 75 yo
- CD123(+) blasts
- Noalternativecurativetherapies,
ineligible for or declining alloHSCT
- ifrelapsedpostprioralloHSCTmust,
be off immune suppression at least 4 wks,
and have no evidence of GvHD
RR AML
- 2 – 65 yo
- CD123(+) by flow cytometry of IHC,
and >80% of blasts CD123(+)
RR AML
- > 6 mo
- Blastspositiveforanyof;
CD33, CD38, CD56, CD117, CD123, CD34
or Muc1 by cytology or genetic testing
Location
The University of Pennsylvania, PA, USA
City of Hope Medical Center, CA, USA
MD Anderson Cancer Center, TX, USA
MD Anderson Cancer Center, TX, USA
Fengtai District, Beijing Shi, China
The General Hospital of Western Theater Command, Chengdu, China
Fujian Medical UniversityUnionHospital, Fujian, China
307 Hospital of PLA, Beijing, China
Hebei Yanda Ludaopei Hospital, Hebei, China
Southern Medical University ZhujiangHospital, Guangdong, China
Trial number
NCT03766126
NCT02159495
NCT03190278
NCT03126864
NCT03114670
NCT03795779
NCT03631576
NCT03556982
NCT03796390
NCT03473457
Intervention
Autologous lentivirally transduced
anti CD123 CARTs (CD123CAR-41BB-CD3 )
Autologous lentivirally transduced anti CD123 CARTs (CD123CAR-CD28-CD3 -EGFRt)
Universal (TCR KO) allogeneic
anti CD123 CARTs (UCART123)
Autologous lentivirally transduced anti CD33CARTs
Strategy to mitigate potential adverse events including myeloablation
- Fractionated dosing of CART-123
- Patient must have a suitably matched donor or
stem cell source available, alloHSCT
expected to be required in responding patients
- EGFRt in CAR construct allows for in vivo eradication of CART population if needed with anti-EGFR mAb
- Patient must have a suitably matched donor or stem cell source available
- TCR KO to reduce risk of GvHD from allogeneic CARTs
- Patient must have a suitably matched donor or stem cell source available
- Incremental dosing of CART-33 (starting dose in both cohorts is >1.5 x105/kg and <4.5 x105/kg)
Allogeneic
(donor derived) lentivirally transduced anti-CD123 CARTs (CD123CAR-41BB-CD3 -EGFRt)
- EGFRt in CAR construct allows for in vivo eradication of CART population if needed with anti-EGFR mAb
Lentivirally - transduced anti CD33
and CLL1 compound
CARTs*
Anti CD123 and CLL1 - compoundCARTs*#
Allogeneic or - autologous
anti CD123 CARTs#
Autologous - lentivirally
transduced anti CD123 CARTs
CARTs targeting - CD33, CD38, CD56,
CD117,CD123,CD34or Muc1 *#
Not stated
Not stated
Not stated
Not stated
Not stated
haematologica | 2019; 104(7)
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