Table 3.
Current early-phase clinical trials for children with relapsed/refractory AML.
| Targeted therapy |
Target | Chemotherapy combination |
Age |
Clinicaltrials.gov identifier |
Study group | Notes |
|---|---|---|---|---|---|---|
| Small molecule inhibitors | ||||||
| venetoclax | BCL-2 | cytarabine +/− idarubicin | 2 - 20 years | NCT03194932 | SJCRH | ALL also eligible |
| venetoclax | BCL-2 | FLA + GO | 29 days - 21 years | NCT05183035 | LLS PedAL/EuPAL | CD33+ AML |
| selinexor, venetoclax | XPO1, BCL-2 | FLA/FLAG | ≤ 30 years | NCT04898894 | SJCRH | ALAL also eligible |
| gilteritinib | FLT3 | gilteritinib, FLAG | 6 months - 21 years | NCT04240002 | Astellas | FLT3-ITD or mutation |
| quizartinib | FLT3 | FLA + etoposide | 1 month - 21 years | NCT03793478 | ITCC/COG | FLT3-ITD or mutation |
| pexidartinib | FLT3 | 3 - 35 years | NCT02390752 | NCI | ALL and solid tumor also eligible | |
| MRX-2843 | FLT3 | ≥ 12 years | NCT04872478 | Meryx | ALL and MPAL also eligible | |
| enasidenib | IDH2 | 2 - 18 years | NCT04203316 | COG | IDH2 mutation | |
| pevonedistat | NEDD8 | azacytidine + FLA | 1 month - 21 years | NCT03813147 | COG/PEP-CTN | active, not recruiting |
| ALRN-6924 | MDM2/MDMX | +/− cytarabine | 1 - 21 years | NCT03654716 | DFCI | CNS and solid tumors; lymphoma and leukemia also eligible |
| idasanutlin | MDM2 | FLA or venetoclax | ≤ 30 years | NCT04029688 | Hoffmann-La Roche | ALL and solid tumor also eligible |
| revumenib (SNDX-5613) | menin | ≥ 30 days | NCT04065399 | Syndax | KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation; KMT2A-rearranged ALL also eligible | |
| revumenib | menin | FLA | ≥ 30 days | NCT05326516 | Syndax | KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation; KMT2A-rearranged ALL or MPAL also eligible |
| revumenib | menin | decitabine + cedazuridine (ASTX727) + venetoclax | ≥ 12 years | NCT05360160 | MDACC | MPAL also eligible |
| niclosamide | CREB | cytarabine | 2 - 25 years | NCT05188170 | Stanford University | ALAL also eligible |
| Antibody and cellular immunotherapies | ||||||
| GO | CD33 | Liposomal daunorubicin and cytarabine | ≤ 21 years | NCT04915612 | MDACC | CD33+ AML |
| CD33 CAR T cells | CD33 | fludarabine + cyclophosphamide LD | 1 - 35 years | NCT03971799 | CIBMTR multi-site | CD33+ AML |
| CD33xCD3 bispecific antibody | CD33xCD3 | 2 - 21 years | NCT05077423 | Y-mAbs Therapeutics, COG/PEP-CTN | study terminated early due to financial decision by sponsor | |
| CD33 CAR T cells (DARIC) | CD33 | rapamycin (activates DARIC) | ≤ 30 years | NCT05105152 | SCH | study terminated before expansion cohort due to financial decision by sponsor |
| flotetuzumab | CD123xCD3 | NCT04158739 | COG/PEP-CTN | active, not recruiting | ||
| CD123CART | CD123 | fludarabine + cyclophosphamide LD, rituximab for T cell termination | ≤ 21 years | NCT04318678 | SJCRH | CD123+ AML/MDS; ALL and BPDCN also eligible |
| CD123CART | CD123 | LD chemotherapy (fludarabine, cyclophosphamide) | 1 - 29 years | NCT04678336 | CHOP | CD123+ AML |
| SAR443579 (NK cell engager) | CD123 | ≥ 12 years | NCT05086315 | Sanofi | B-ALL and high-risk MDS also eligible | |
| CLL-1 CAR T cells | CLL-1 (CLEC12A, CD371) | fludarabine + cyclophosphamide LD | ≤ 75 years | NCT04219163 | BCM/TCH | CLL-1+ AML |
| CIML NK cells | AML cells | FLAG or fludarabine + cyclophosphamide LD | ≥ 1 year | NCT03068819 | WUSTL | post-HSCT relapse |
| CIML NK cells | AML cells | fludarabine + cyclophosphamide LD | ≥ 1 year | NCT04024761 | DFCI | post-HSCT relapse |
ALAL = acute leukemia of ambiguous lineage, BCM/TCH = Baylor College of Medicine/Texas Children’s Hospital, BPDCN = blastic plasmacytoid dendritic cell neoplasm, CHOP = Children's Hospital of Philadelphia, CREB = cAMP response element binding protein, CIBMTR = Center for International Blood and Marrow Transplant Research, CIML = cytokine-induced memory-like, COG = Children's Oncology Group, DARIC = dimerizing agent-regulated immune-receptor complex, DFCI = Dana-Farber Cancer Institute, FLA = fludarabine/cytarabine, FLAG = fludarabine/cytarabine + g-csf, HSCT = hematopoietic stem cell transplant, ITCC = Innovative Therapies for Childhood Cancer consortium, LD = lymphodepleting chemotherapy, LLS PedAL/EuPAL = Leukemia & Lymphoma Society Pediatric Acute Leukemia and European Pediatric Acute Leukemia consortium, MDS = myelodysplastic syndrome, MPAL = mixed phenotypic acute leukemia, NCI = National Cancer Institute, SCH = Seattle Children's Hospital, SJCRH = St Jude Children's Research Hospital, WUSTL = Washington University in St Louis.