Table 6.
Active clinical trials of immune checkpoint inhibitors in myeloid neoplasms.
| Disease type and inclusion criteria | Drug type and target | Outcome measures/endpoints | Estimated enrollment | Clinical trials identifier | Trial status |
|---|---|---|---|---|---|
| R/R AML High-risk MDS |
Ipilimumab (anti-CTLA-4) | Primary: DLT, BP Secondary: CR, PR, HI, BP, OS, and PFS |
42 | NCT01757639 | Ongoing (completion late 2016) |
| R/R AML R/R MDS |
Decitabine (HMA) + ipilimumab | Primary: MTD Secondary: ORR, PFS, OS, BP, and GvHD |
48 | NCT02890329 | Recruiting (estimated completion late 2018) |
| AML, MDS, MPN, CML, MM, HL, NHL, CLL (after aHSCT) | Nivolumab vs. ipilimumab (anti-PD-1) | Primary: MTD Secondary: ORR, PFS, OS, and BP |
113 | NCT01822509 | Recruiting (estimated completion late 2018) |
| R/R AML Secondary AML from MDS or CMML |
AZA (HMA) + nivolumab vs. AZA + nivolumab + ipilimumab | Primary: MTD Secondary: ORR |
182 | NCT02397720 | Recruiting (estimated completion early 2019) |
|
De novo MDS MDS after HMA failure |
Nivolumab vs. ipilimumab vs. nivolumab + ipilimumab | Primary: ORR, CR, PR, and HI | 120 | NCT02530463 | Recruiting (estimated completion mid 2021) |
| AML, MDS (after aHSCT) | Nivolumab vs. ipilimumab vs. nivolumab + ipilimumab | Primary: safety Secondary: toxicity, HI, BP, CR, and PFS |
21 | NCT02846376 | Recruiting (estimated completion mid 2022) |
| cp or ap CML (resistance to ≥2 previous TKIs) | Dasatinib (TKI) + nivolumab | Primary: DLT, SAE Secondary: MMR and MR |
69 | NCT02011945 | Ongoing (estimated completion mid 2019) |
| AML in remission with high risk for relapse | Nivolumab | Primary: RFS | 30 | NCT02532231 | Recruiting (estimated completion late 2018) |
| AML in remission not eligible for aHSCT | Nivolumab | Primary: PFS Secondary: AE, OS, and NRM |
80 | NCT02275533 | Recruiting (estimated completion mid 2019) |
| AML High-risk MDS |
Idarubicin + cytarabine + nivolumab | Primary: MTD Secondary: EFS |
75 | NCT02464657 | Recruiting (estimated completion mid 2019) |
|
De novo AML High-risk MDS |
AZA vs. AZA + nivolumab vs. AZA + midostaurin (multi-TKI) vs. decitabine + cytarabine | Primary: OS Secondary: CR, CRi, EFS, AE, and RFS |
1,670 | NCT03092674 | Recruiting (estimated completion mid 2022) |
| MDS | AZA + durvalumab (MEDI4736, anti-PD-L1) + tremelimumab (anti-CTLA-4) | Primary: DLT, safety Secondary: PK, BP, DOR, HI, PFS, OS, ADA, and QOL |
73 | NCT02117219 | Recruiting (estimated completion mid 2020) |
| Previously untreated high-risk MDS De novo AML in elderly patients (≥65 years) not eligible for aHSCT |
AZA + durvalumab | Primary: ORR, PR, CR, CRi, HI Secondary: AE, DOR, RFS, PFS, TBR, TTT, PK, and OS |
182 | NCT02775903 | Recruiting (estimated completion mid 2019) |
| R/R AML De novo AML in patients not eligible for curative therapy |
AZA + pembrolizumab (anti-PD-1) | Primary: MTD Secondary: CR, CRi |
40 | NCT02845297 | Recruiting (estimated completion mid 2020) |
| R/R AML | Decitabine + pembrolizumab | Primary: feasibility Secondary: efficacy |
15 | NCT02996474 | Recruiting (estimated completion mid 2019) |
| Refractory AML | Pembrolizumab | Primary: BP, safety, and tolerability Secondary: OS and BP |
10 | NCT03291353 | Not yet recruiting (estimated completion mid 2022) |
| AML in CR in patients ≥60 years | Pembrolizumab | Primary: RFS and AE Secondary: OS |
40 | NCT02708641 | Recruiting (estimated completion mid 2021) |
| R/R AML | High-dose cytarabine + pembrolizumab | Primary: CR Secondary: toxicity, ORR, RFS, PFS, and OS |
37 | NCT02768792 | Recruiting (estimated completion mid 2025) |
| Non-favorable risk AML in CR | Fludarabine + melphalan + autologous HSCT + pembrolizumab | Primary: 2-year relapse risk Secondary: safety |
20 | NCT02771197 | Recruiting (estimated completion late 2020) |
| AML, MDS, and ALL (relapsed after aHSCT) | Pembrolizumab | Primary: CR and PR Secondary: patients alive with or without disease at 1 year |
20 | NCT03286114 | Not yet recruiting (estimated completion late 2021) |
| AML, MDS, HL, and NHL (relapsed after aHSCT) | Pembrolizumab | Primary: AE Secondary: DOR, CR, PR, ORR, OS, and BP |
26 | NCT02981914 | Recruiting (estimated completion early 2020) |
| MDS R/R MM, HL, NHL, MLBCL, FL, and DLBCL |
Pembrolizumab | Primary: AE, ORR, and CR | 222 | NCT01953692 | Ongoing, not recruiting (estimated completion mid 2018) |
| R/R AML De novo AML in patients not eligible for curative therapy |
Atezolizumab (anti-PD-L1) + guadecitabine | Primary: AE, CR, CRi, CRp, and DOR Secondary: OR, EFS, LFS, OS, MRD, ADA, BP, and PK |
40 | NCT02892318 | Recruiting (estimated completion early 2019) |
| AML in patients ≥60 years | BL-8040 (CXCR4 inhibitor) + atezolizumab | Primary: RFS | 60 | NCT03154827 | Recruiting (estimated completion early 2022) |
| High-risk MDS R/R CMML |
Atezolizumab + guadecitabine (HMA) | Primary: DLT, CR Secondary: AE, SAE, ORR, OS, HI, PFS, and TBR |
72 | NCT02935361 | Recruiting (estimated completion late 2021) |
| MDS | Atezolizumab vs. atezolizumab + AZA | Primary: DLT, AE Secondary: OR, PK, DOR, TTT, PFS, HI, and QOL |
100 | NCT02508870 | Recruiting (estimated completion early 2019) |
| R/R AML De novo AML in patients not eligible for curative therapy High-risk MDS |
Decitabine + PDR001 (anti-PD-1) vs. decitabine + MBG453 (anti-TIM-3) vs. decitabine + PDR001 + MBG453 | Primary: DLT, AE, and SAE Secondary: ORR, PFS, DOR, BP, and PK |
70 | NCT03066648 | Recruiting (estimated completion mid 2019) |
| R/R AML | PF-04518600 (OX-40 agonist mAb) vs. PF-04518600 + avelumab (anti-PD-L1 mAb) vs. PF-04518600 + AZA vs. PF-04518600 + utomilumab (4-1BB agonist mAb) vs. avelumab + utomilumab vs. PF-04518600 + avelumab + AZA vs. GO + glasdegib (smoothened inhibitor) vs. glasdegib + avelumab | Primary: AE and CR Secondary: DFS, MRD, and OS |
138 | NCT03390296 | Recruiting (estimated completion late 2023) |
| R/R AML | AZA + avelumab | Primary: MTD and DLT Secondary: ORR |
58 | NCT02953561 | Recruiting (estimated completion early 2021) |
| De novo AML in patients not eligible for curative therapy | Decitabine + avelumab | Primary: safety and AE Secondary: CR, CRi, and OS |
15 | NCT03395873 | Recruiting (estimated completion late 2020) |
AE, adverse events; aHSCT, allogeneic hematopoietic stem cell transplantation; ADA, anti-drug antibodies; AML, acute myeloid leukemia; ap, accelerated-phase; AZA, 5-azacytidine; BP, blood parameters; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; CMML, chronic myelomonocytic leukemia; cp, chronic-phase; CR, complete remission; CRi, complete remission with incomplete recovery; CRp, complete remission with incomplete platelet recovery; CTLA-4, cytotoxic T lymphocyte antigen-4; DFS, disease-free survival; DLBCL, diffuse large B cell lymphoma; DLT, dose-limiting toxicity; DOR, duration of response; EFS, event-free survival; GO, gemtuzumab ozogamicin; GvHD, graft-versus-host disease; HI, hematological improvement; HL, Hodgkin lymphoma; HMA, hypomethylating agent; mAb, monoclonal antibody; MDS, myelodysplastic syndrome; MLBCL, mediastinal large B cell lymphoma; MM, multiple myeloma; MMR, major molecular response; MPN, myeloproliferative neoplasm; MR, molecular response; MRD, minimal residual disease; MTD, maximum tolerated dose; NRM, non-relapse mortality; OR, objective response; ORR, overall response rate; NHL, non-Hodgkin lymphoma; OS, overall survival; PD-1, programmed death protein-1; PFS, progression-free survival; PK, pharmacokinetics; PR, partial remission; QOL, quality of life; RFS, relapse-free survival; R/R, refractory/relapsed; SAE, serious adverse events; TBR, time to best response; TIM-3, T cell immunoglobulin and mucin domain-containing molecule 3; TKI, tyrosine kinase inhibitor; TTT, time to transformation.
Data from http://ClinicalTrials.gov (Accessed: March 04, 2018).