Table 1.
Clinical trials using autophagy modulators for myeloid leukemias.
| Agent | Regulation of Autophagy | Disease | Trial ID | Phase | Patients, N | Median Age (years) | Other Treatments | Clinical Response (N) | References |
|---|---|---|---|---|---|---|---|---|---|
| Bortezomib | induction | Elderly AML/relapsed AML | NCT00382954 | 1 | 20 | 68 (elderly) 58 (relapsed) |
once weekly idarubicin | CR 20% (4/20) PR 5% (1/20) |
Howard et al. 2013 [159] |
| Elderly AML | NCT00742625 | 1/2 | 95 | 67 | 3 + 7 (daunorubicin + cytarabine) | CR 65% (62/95) CRp 4% (4/95) PR 2% (2/95) |
Attar et al. 2013 [160] | ||
| Relapsed/refractory AML | NCT00666588 | 2 | 46 | Arm A: 10 Arm B: 6.1 |
Arm A: IDA + LDAC Arm B: ETP + HDAC |
(Arm A) CR 29% (Arm B) CR 43% |
Horton et al. 2014 [162] | ||
| Relapsed APL | NCT01950611 | 2 | 22 | 26.5 | ATRA + Arsenic trioxide | Molecular remission 90.5% (19/21) |
Kulkarni et al. 2020 [161] | ||
| Temsirolimus | induction | Relapsed/refractory AML | NCT00775593 | 2 | 53 | 69 | Lower-dose clofarabine | CR 8% (4/53) CRi 13% (7/53) PR 2% (1/53) |
Amadori et al. 2011 [165] |
| RAD001 (everolimus) | induction | First relapsed AML | NCT01074086 | 1b | 28 | 53.5 | 3 + 7 (daunorubicin + cytarabine) | CR 68% (19/28) | Park et al. 2013 [166] |
| Elderly AML | NCT00636922 | 1b | 24 | 74 | Low-dose Ara-C | CR+CRi 25% (6/24) PR 4.2% (1/24) |
Tiong et al. 2018 [167] | ||
| Sirolimus | induction | High-risk AML | NCT00780104 NCT01184898 | 1/2 | 51 | 60 | MEC (mitoxantrone, etoposide and cytarabine) | CR 33% (17/51) CRi 2% (1/51) PR 12% (6/51) |
Kasner et al. 2018 [163] |
| BEZ235 | induction | Relapsed/refractory AML CML-BP | NCT01756118 | 1 | 24 (AML: 12) (CMLBP: 1) | 61 * | none | clear response 12.5% (3/24) ** |
Lang et al. 2020 [154] |
| Devimistat | induction | Relapsed/refractory AML | NCT01768897 | 1 | 67 | 60 | high dose cytarabine + mitoxantrone | CR 42% (26/62) CRi 8% (5/62) |
Pardee et al. 2018 [171] |
| induction | Relapsed/refractory AML | NCT02484391 | 2 | 48 | 64 | high dose cytarabine + mitoxantrone | CR 34% (15/44) CRi 13% (6/44) |
Anderson et al. 2022 [170] | |
| induction | Relapsed/refractory AML | NCT03504410 | 3 | 200 | 65 | high dose cytarabine + mitoxantrone | CR 20.4% | Pardee et al. 2024 [172] | |
| Chidamide | inhibition | Relapsed/refractory AML | NCT02886559 | 1/2 | 93 | 40 | decitabine, CAG | CR 26% (24/93) CRi 20% (19/93) |
Wang et al. 2020 [174] |
| Hydroxychloroquine | inhibition | CML-CP | NCT01227135 | 2 | 32 | 50 | Imatinib | IM/HCQ: MMR 92% IM: MMR 80% |
Horne et al. 2020 [148] |
CR, complete remission; CRi, complete remission with incomplete hematopoietic recovery; CRp, complete remission with imcomplete platelet recovery; PR, partial response; ATRA, all trans retinoic acid; IDA, idarubicin; ETP, etoposide; LDAC, low-dose Ara-C; HDAC, high-dose Ara-C; IM, imatinib; HCQ, hydroxychloroquine; MMR, major molecular response; CAG, low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor; * Median age of all study participants, ** Response was seen only in ALL patients.