Table 3.
Ongoing clinical trials in RS.
| Reference | Drugs | Study features | Patients enrollment | Protocol | Primary outcome | Secondary outcome |
| NCT02846623 | Atezolizumab + Obinutuzumab + Venetoclax | Phase II open label clinical trial | 65 R/R CLL/SLL and RS | A + O + V for 14 cycles of 28 days vs A+ O + V for 25 cycles of 28 days. | Minimal residual disease negative rate | AEs, best ORR, CRR, duration of response, PFS, OS |
| NCT04271956 | Zanubrutinib + Tislelizumab | Prospective phase II open label multicenter clinical trial | 45 RS | T + Z for induction and consolidation (6 cycles each), then maintenance until DP or allo-SCT | ORR after induction according to the Lugano Classification | ORR after induction therapy (IWCLL criteria) ORR after consolidation therapy, PFS, OS, TTNT, duration of response, AEs |
| NCT03884998 | Copanlisib+ Nivolumab | Phase I open label clinical trial | 15 RS or Transformed Indolent NHL | C + N for 12 cycles of 28 days in the absence of DP or UT. | Incidence of dose-limiting toxicities & AEs | ORR, duration of treatment, PFS, OS |
| NCT02332980 | Pembrolizumab + Idelalisib or Pembrolizumab + Ibrutinib or Pembrolizumab alone | Phase II open label clinical trial | 68 R/R CLL or other low-grade B NHL | P for 12 cycles, or P + I or P + Id for 12-24 cycles in the absence of DP or UT. | Confirmed response | CRR, AEs incidence, ORR, PFS, survival |
| NCT03892044 | Duvelisib and Nivolumab | Phase I open label clinical trial | 44 RS or transformed FL | N. + D for 28 days cycles until DP or UT. | Maximal Tolerated Dose | ORR, PFS, OS |
| NCT04082897 | Atezolizumab and Obinituzumab and Venetoclax | Phase II open-labeled, uncontrolled, multicenter clinical trial | 28 RS | A + O + V from cycle 1 to 8; A + V from cycle 9 to 18; V only from cycle 19 to 35 | ORR | AEs (CTCAE v4), CRR, duration of response, PFS, OS |
| NCT02420912 | Nivolumab and Ibrutinib | Phase II open-labelled non-randomized clinical trial | 72 R/R or high-risk untreated CLL, SLL, or RS | For RS: N+ I for 1 or 2-24 cycles if no DP or UT. | CR or CR with incomplete BM recovery | AEs (CTCAE v4), OS, PFS |
| NCT03321643 | Atezolizumab and Rituximab and Oxaliplatin and Gemcitabine | Phase I open-label sign group assignment clinical trial | 30 transformed DLBCL (including RS) | Induction: [R + Ox + Gem] + A starting cycle 2. Maintenance: R + A | AEs (CTCAE v5), Maximal Tolerated Dose | CRR, best ORR, biomarker analysis |
| NCT02362035 | Acalabrutinib and Pembrolizumab | Phase Ib/II open label clinical trial | 161 B-cell malignancies | UD | AEs | UD |
| NCT02535286 | Ublituximab and Umbralisib and Cosibelimab | Phase I open label clinical trial | 20 R/R CLL or RS | Ub followed by maintenance infusions of Um. + Cos | AEs | ORR |
| NCT03121534 | Blinatumomab | Phase II open label clinical trial | 10 RS | Induction 8 weeks. If objective response: consolidation 4 weeks | ORR | Toxicity |
| NCT03931642 | R-CHOP and Blinatumomab | Phase II open label clinical trial | 35 RS (DLBCL) | 2 R-CHOP cycles then Bl if CR and no measurable lesion | CRR | AEs (CTCAE v4), OR, CR |
| NCT02924402 | XmAb13676 | Phase I open label clinical trial | 66 non B-cell NHL, CLL/SLL/RS. | XmAb13676 administered weekly up to 8 weeks | AEs (CTCAE v4), max tolerated or recommended dose | / |
A, atezolizumab (anti-PD-L1); Ac, acalabrutinib (BTK inhibitor); AEs, adverse events; CTCAE, Common Terminology Criteria for Adverse Events; allo-SCT, allogeneic stem cell transplantation; BM, bone marrow; Bl, blinatumomab (anti-CD19 and anti-CD3 bispecific antibody); BTK; Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; Cop, copanlisib (PI3Kα,δ inhibitor); Cos, cosibelimab (anti-PD-L1); CR, complete response; CRR, complete response rate; D, duvelisib (inhibitor of PI3Kδ and PI3Kγ); DLBCL, diffuse large B cell lymphoma; FL, follicular lymphoma; DP, disease progression; Gem, gemcitabine; I, ibrutinib (BTK inhibitor); Id, idelalisib (PI3Kδ Inhibitor); IWCLL, International Workshop on Chronic Lymphocytic Leukemia; N, nivolumab (anti-PD-1); NHL, non-Hodgkin lymphoma; O, obinutuzumab (anti-CD20); ORR, overall response rate; OS, overall survival; Ox, oxaliplatin; P, pembrolizumab (anti-PD-1); PFS, progression-free survival; R, rituximab (anti-CD20); R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone; R/R, relapsed or refractory; RS, Richter syndrome; SLL, small lymphocytic lymphoma; T, tislelizumab (anti-PD-1); TTNT, time to next treatment; Ub, ublituximab (anti-CD20); UD, undetermined; Um, umbralisib (anti-PI3Kδ and CK1e); UT, unacceptable toxicity; V, venetoclax (anti-BCL-2); X, XmAb13676 (anti-CD20 and anti-CD3 bispecific antibody); Z, zanubrutinib (BTK inhibitor).