Table 1.
Overview of studies evaluating subcutaneous rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia
| Study name | Study design | Patient population | Treatment regimen | Number of patients |
|---|---|---|---|---|
| SparkThera [45] (NCT00930514) | Phase Ib randomized, multicenter, two-stage dose-finding and dose-confirmation study | Previously untreated or treated FL |
Stage 1 dose-finding: single cycle of R-SC test dose (375, 625, or 800 mg/m2) (control arm: R-IV 375 mg/m2), followed by R-IV maintenance (2 years) Stage 2 dose confirmation: R-SC 1400 mg q2 m for 12 cycles or q3 m for 8 cycles (control arm: ≤12 cycles R-IV 375 mg/m2) |
Stage 1: 124 (108 R-SC, 16 R-IV) Stage 2: 154 (77 R-SC, 77 R-IV) |
| SABRINA [44, 47] (NCT01200758) | Phase III randomized, multicenter, two-stage study | Previously untreated FL |
Induction: 8 × q3w cycles of rituximab administered in combination with CHOP or CVP. Cycle 1 R-IV 375 mg/m2; Cycles 2–8 R-SC 1400 mg (control arm: cycles 2–8 R-IV 375 mg/m2) Maintenance: R-SC 1400 mg q8w for 2 years for patients with ≥PR to induction (control arm: R-IV 375 mg/m2) |
Stage 1: 127 (63 R-SC, 64 R-IV) Stage 2: 283 Stage 1 + 2 total: 410 (205 R-SC, 205 R-IV) |
| SAWYER [46, 48] (NCT01292603) | Phase Ib, multicenter, two-part, dose-finding and dose confirmation study | Previously untreated CLL |
Part 1 dose-finding: single cycle of R-SC test dose (1400, 1600, 1870 mg) with FC at cycle 6 Part 2 dose confirmation: 6 × q4w cycles of rituximab administered in combination with FC Cycle 1 R-IV 375 mg/m2; cycles 2–6 R-SC 1600 mg (control arm: cycles 2–6 R-IV 500 mg/m2) |
Part 1: 64 (56 R-SC) Part 2: 176 (88 R-SC, 88 R-IV) |
| MabEase [49, 57] (NCT01649856) | Phase IIIb randomized, open-label, multicenter study | Previously untreated DLBCL |
8 cycles of rituximab administered in combination with CHOP (6 or 8 cycles) q2w or q3w. Cycle 1 R-IV 375 mg/m2; Cycles 2–8 R-SC 1400 mg (control arm: Cycles 2–8 R-IV 375 mg/m2) |
576 (381 SC, 195 IV) |
| PrefMab [51] (NCT01724021) | Phase IIIb, open-label, randomized, multicenter, crossover study | Previously untreated DLBCL or FL |
8 cycles of rituximab administered in combination with CHOP, CVP, or bendamustinea. Arm A: Cycle 1 R-IV 375 mg/m2; Cycles 2–4 R-SC 1400 mg; Cycles 5–8 R-IV 375 mg/m2 Arm B: Cycles 1–4 R-IV 375 mg/m2; Cycles 5–8 R-SC 1400 mg |
743 (372 Arm A, 371 Arm B) |
|
MabCute [52] (NCT01461928) |
Phase IIIb randomized, multicenter study | Relapsed/refractory iNHL |
Induction: 8 cycles of rituximab q3w/q4w administered in combination with 6–8 cycles of CHOP or CVP. Cycle 1 R-IV 375 mg/m2; Cycles 2-8 R-SC 1400 mg. Maintenance I: R-SC 1400 mg q8w for 2 years in patients with ≥ PR following induction Maintenance IIc: R-SC 1400 mg q8w until disease progression (control arm: observation) |
216b |
| MabRella [54] (NCT01987505) | Phase IIIb, open-label, single-arm, safety umbrella study | Previously untreated DLBCL or FL |
FL/DLBCL induction: q2w, q3w or q4w rituximab in combination with standard chemotherapy for 4– 7 cycles Cycle 1 R-IV 375 mg/m2; Cycles 2-8 R-SC 1400 mg FL maintenance: R-SC 1400 mg q2 m for 6–12 cycles |
336 |
C trough trough (pre-dose) concentration, CHOP cyclophosphamide, vincristine, doxorubicin, prednisone, CLL chronic lymphocytic leukemia, CR complete response, CVP cyclophosphamide, vincristine, prednisone, DLBCL diffuse large B-cell lymphoma, FC fludarabine and cyclophosphamide, FL follicular lymphoma, I indolent, IV intravenous, NHL non-Hodgkin lymphoma, PR partial response, q2 m every 2 months, q3 m every 3 months, q2w once every 2 weeks, q3w once every 3 weeks, q4w once every 4 weeks, q8w once every 8 weeks, R rituximab, SC subcutaneous
aPatients were randomized to receive either rituximab SC at cycles 2–4 (after the first cycle rituximab IV) or rituximab IV at cycles 1–4. After the fourth cycle, patients were crossed over to the alternative route of administration for the remaining four cycles
bAt interim analysis; more currently enrolled
cPatients maintaining CR/PR at the end of the standard 2 years of rituximab SC maintenance will be randomized to additional maintenance treatment with rituximab SC or observation (Maintenance II)