Table 1.
Clinical studies of TKI-combined therapies and immune strategies for CML.
| Therapies | NCT Number | Phase | Patient Characteristics | Status | Primary Objective | Results |
|---|---|---|---|---|---|---|
| TKI + Interferon | ||||||
| Imatnib + interferon | NCT01933906 | 1 | CP-CML (n = 12) | Completed | Safety and tolerability | NDP |
| NCT01227356 | 2 | CP-CML (n = 112) | Completed | MMR at 12 months | NDP | |
| NCT00219739 (SPIRIT) | 3 | CP-CML (n = 789) | Completed (1, 2) | OS | 14% vs. 25%: MR4.0 at M12 (IM vs. IM + IFN 90 μg/week); 10% vs. 28%: MR4.0 (IM vs. IM+IFN 45 μg/week) | |
| NCT00055874 | 3 | CP-CML (n = 1551) | Completed (3, 4) | OS; PFS; molecular response | 59% vs. 44% vs. 46%: MMR at M12 (IM 800 mg/d vs. IM 400 mg/d vs. IM 400 mg/d + IFN) | |
| Nilotinib + interferon | NCT01220648 (NICOLI) | 1 | CP-CML (n = 4) | Completed (5) | MTD of IFN | NDP |
| NCT01294618 (NILOPEG) | 2 | CP-CML (n = 41) | Completed (6) | CMR at 12 months | 17%: MR 4.5 at M12 24%: grade 3–4 neutropenias 73%: remained on IFN therapy at 1 year | |
| NCT02001818 (PInNACLe) | 2 | CP-CML (n = 100) | Recruiting | level of BCR-ABL at 24 months | NDP | |
| NCT01657604 (TIGER) | 3 | CP-CML (n = 717) | Active, not recruiting | MMR at 18 months | NDP | |
| NCT02201459 (PETALs) | 3 | CP-CML (n = 200) | Unknown | MR4.5 at 12 months | NDP | |
| Dasatinib + interferon | NCT01872442 | 2 | CP-CML (n = NDP) | Completed | MR4.5 at 12 months | NDP |
| NCT01725204 (NordCML007) | 2 | CP-CML (n = 40) | Completed (7) | MMR at 12 months | 84%: remained on Peg-IFN at M12 10, 57, 84 and 89%: MMR at M3, M6, M12 and M18 46%: MR4.0 at M12 27%: MR4.5 at M12 | |
| Bosutinib + interferon | NCT03831776 (BosuPeg) | 2 | CP-CML (n = 212) | Recruiting | MR4.0 at 12 months | NDP |
| TKI + Venetoclax/ABT-199 | ||||||
| Dasatinib + venetoclax | NCT02689440 | 2 | CP-CML (n = 140) | Recruiting (8, 9) | MMR at M12 | 81%: MMR; 55%: MR4.0; 49%: MR4.5; 80%: required dose reduction; none: disease progression at M24 |
| Ponatinib + venetoclax | NCT03576547 | 1/2 | Ph+ relapsed/refractory ALL/CML (n = 38) | Recruiting | MTD of combination therapy | NDP |
| NCT04188405 | 2 | Ph+ AML or BP CML (n = 30) | Recruiting | CR or CRi at the end of two cycles of treatment (each cycle is 28 days) | NDP | |
| TKI + Ruxolitinib | ||||||
| Nilotinib + ruxolitinib | NCT01702064 | 1 | CML patients with evidence of molecular disease (n = 11) | Completed (10) | MTD of ruxolitinib with nilotinib at M6 | 1/11: grade 3/4 hypophosphatemia; 36%: grade 1/2 anemia; 4/10: have undetectable BCR-ABL transcripts |
| NCT02253277 (CoRNea) | 1 | CML and Ph+ ALL (n = 5) | Completed | DLTs during cycle 1 (up to day 28) | NDP | |
| NCT01914484 | 1/2 | TKI resistant CML or Ph+ ALL (n = 4) | Completed | MTD at M6 | NDP | |
| Das/Nil + ruxolitinib | NCT03654768 | 2 | CP-CML (n = 84) | Recruiting | MR4.5 at M12 | NDP |
| either prior TKI + ruxolitinib | NCT03610971 | 2 | CP and previously attempted to discontinue TKI therapy (n = 14) | Recruiting | TFR rate at M12 | NDP |
| TKI + Asciminib | ||||||
| Imatinib + asciminib | NCT03578367 | 2 | pre-treated CP-CML (n = 80) | Recruiting | MR4.5 at 48 weeks | NDP |
| Dsatinib + asciminib | NCT03595917 | 1 | Ph+ B-ALL or CML (n = 34) | Recruiting | MTD of ABL001 after 42 Days | NDP |
| Bosutinib + asciminib | NCT03106779 | 3 | CML-CP previously treated with two or more TKIs (n = 233) | Active, not recruiting | MMR rate of ABL001 versus bosutinib at 24 weeks | NDP |
| IM/NIL/DAS + asciminib | NCT02081378 | 1 | CML or Ph+ ALL relapsed/refractory/intolerant to TKIs (n = 330) | Recruiting | DLTs during the first cycle of treatment (first cycle is 28 days) | 48%: MMR by 12 months; MMR was achieved/maintained by 12 months in five patients (28%) with a T315I mutation |
| NCT03906292 (CMLXI) | 2 | newly diagnosed CML (n = 120) | Recruiting | MR4.0 at M12 | NDP | |
| TKI + Pioglitazone | NCT02852486 (EDI-PIO) | 2 | CML with DMR (n = 31) | Active, not recruiting (11) | TFR time after IM discontinuation | NDP |
| NCT02889003 (PIO2STOP) | 2 | CML (n = 26) | Recruiting | Treatment-related adverse events and treatment-free survival up to 24 months | NDP | |
| NCT02767063 (ACTIW) | 1 | CP-CML in CCR (n = 100) | Recruiting | DMR at M12 | NDP | |
| TKI + Vaccines | ||||||
| BCR-ABL1 as a specific antigen | ||||||
| e13a2 | NCT00466726 (CML0206) | 2 | CML (n = 57) | Completed (12) | Reduction by at Least 50% of peripheral blood BCR-ABL/ABL ratio at 6 and 9 months | 9%: a mild fever; 67%:CD4+ T cell proliferation; 51%: a reduction of ≥50% of pre-vaccine BCR-ABL/ABL values after nine vaccinations; 48%: the reduction was confirmed after 10 vaccinations |
| NCT00004052 | 2 | CML (n = 24) | Completed | Safety and immunogenicity | NDP | |
| e13a2, e14a2 | NCT00428077 | 2 | CP (n = 4) | Terminated | BCR-ABL transcripts in PB every 3 months for 1 year | 1/4: grade 3 acute gastroenteritis; 1/4: grade 2 cataracts |
| NCT00267085 | 2 | CML in remission but with MRD (n = 10) | Completed | One Log Decrease in BCR-ABL at M12 | 1/10: nausea; 1/10: neck pain; 1/10: back pain | |
| LAAs | ||||||
| WT1 | NCT00004918 | 1/2 | CML, AML or MDS (n = 69) | Completed | Adverse event DTOX up to 8 years | NDP |
| TKI + ICB | ||||||
| Nivolumab | NCT01822509 | 1 | Relapsed hematologic malignancies including CML (n = 71) | Active, not recruiting (13) | MTD of nivolumab at 12 weeks | 32% (8/25): ORR 23%: 1-year PFS 56%: OS |
| NCT02011945 | 1 | CML (n = 35) | Completed | DLT of combination therapy during the first 6 weeks | NDP | |
| Avelumab | NCT02767063 (ACTIW) | 1/2 | CP-CML in CCR (n = 100) | Recruiting | DMR at M12 | NDP |
TKI, tyrosine kinase inhibitor; IM, imatinib; NIL, nilotinib; DAS, dasatinib; LAAs, leukemia associated antigens; ICB, immune-checkpoint blockade; OS, overall survival; PFS, Progression-free survival; NDP, No Data Posted; MTD, maximum tolerated dose; IFN, interferon; CMR, complete molecular remissions; DMR, deep molecular response; ALL, Acute lymphoblastic leukemia; AML. Acute Myeloid Leukemia; MDS, Myelodysplastic Syndrome; BP, blast phase; CR, complete remission; Cri, CR with incomplete count recovery; DLTs, dose limiting toxicities; PB, Peripheral blood; DTOX, death or autoimmune toxicity or vascular toxicity at any time; ORR, overall response rate; PFS, progression-free survival.