Rituxan Hycela (Page 7 of 9)
14.2 Diffuse Large B-Cell Lymphoma (DLBCL)
The MabEase study [NCT01649856] enrolled a total of 576 patients with previously untreated CD20-positive DLBCL. Patients were randomized (2:1) to receive either a rituximab product by intravenous infusion, 375 mg/m2 for 8 cycles or 1 cycle of a rituximab product by intravenous infusion 375 mg/m2 followed by 7 cycles of RITUXAN HYCELA 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human), both in combination with up to 6–8 cycles of CHOP chemotherapy, every 14 (CHOP-14) or 21 days (CHOP-21). Randomization was stratified by: age (< 60 years, ≥ 60 years), International Prognostic Index (IPI) risk category (low, low-intermediate, high-intermediate, high), and chemotherapy regimen (CHOP-21 or CHOP-14). The main outcome measure was investigator-assessed complete response rate (CR/CRu) at the end of combination treatment with chemotherapy. Additional outcome measures were time-to-event endpoints (PFS and OS).
Of all randomized patients, the median age was 64 years (range: 18 to 80 years); 54% were male; and 79% were White. The median BSA was 1.83 m2. 31% low risk or 30% low intermediate risk IPI score, 24% high intermediate risk, or 15% high risk IPI score and 42% of patients had Ann Arbor Stage IV disease. A total of 470 patients (82%) received 8 cycles of treatment. Median duration of exposure to treatment was 4.9 months in both treatment groups. The median number of administrations/cycles (RITUXAN HYCELA or rituximab) was 8 in both groups.
The efficacy results for are presented in Table 7. The median observation time was approximately 28 months.
| RITUXAN HYCELA N=381 | Rituximab N=195 | |
|---|---|---|
| ||
| Complete Response Rate (CR/CRu)* | ||
| Number achieving CR/CRu † | 179 | 82 |
| Cr/CRu rate (%, [95% CI]) | 47% [42;52] | 42% [35;49] |
| Difference in rates [95% CI]‡ | 4.9% [-3.6;13.5] | |
| Progression-free survival § | ||
| Number of patients with event | 104 (27%) | 44 (23%) |
| Hazard Ratio [95% CI] (unstratified Cox model) | 1.22 [0.85;1.73] | |
| Overall survival ¶ | ||
| Number of patients with event | 63 (17%) | 29 (15%) |
| Hazard Ratio [95% CI] (unstratified Cox model) | 1.08 [0.70;1.68] | |
14.3 Chronic Lymphocytic Leukemia (CLL)
The SAWYER study [NCT01292603] was a randomized, two-part, open-label, multicenter study that enrolled a total of 176 patients with previously untreated CLL. Patients were randomized (1:1) to receive either a rituximab product by intravenous infusion, 375 mg/m2 , in Cycle 1 followed by up to 5 cycles of rituximab, 500 mg/m2 , or rituximab, 375 mg/m2 , in Cycle 1 followed by subsequent cycles (2–6) of RITUXAN HYCELA 1,600 mg/26,800 Units (1,600 mg rituximab and 26,800 Units hyaluronidase human), both in combination with fludarabine and cyclophosphamide (FC) chemotherapy. The main outcome measure was the non-inferiority of the pharmacokinetic profile of RITUXAN HYCELA compared to rituximab. An additional outcome measure in Part 2 was investigator-assessed response rate.
The median age was 60 years (range: 25 to 78); 65% were males and 96% were White. The median BSA was 1.9 m2 , 62% had Binet Stage B disease and 93% had typical CLL characterization.
The pharmacokinetic results demonstrated that RITUXAN HYCELA 1,600 mg/26,800 Units serum rituximab Ctrough level was non-inferior compared with rituximab at 500 mg/m2 in patients receiving combination treatment with chemotherapy [see Clinical Pharmacology (12.3)].
The efficacy results for Part 2 are presented in Table 8.
| Part 2 | |||
|---|---|---|---|
| RITUXAN HYCELA (N = 88) | Rituximab (N = 88) | ||
| ORR – Overall Response Rate | |||
| CRR – Complete Response Rate | |||
| PFS – Progression-Free Survival | |||
| ORR * | Point estimate | 85.2% (n = 75) | 80.7% (n = 71) |
| 95% CI | [76.1%, 91.9%] | [70.9%, 88.3%] | |
| CRR * | Point estimate | 27.3% (n = 24) | 31.8% (n = 28) |
| 95% CI | [18.3%, 37.8%] | [22.3%, 42.6%] | |
| PFS † | Proportion with PFS event | 34.1% (n = 30) | 42.0% (n = 37) |
| HR 95% CI | 0.76 [0.47%, 1.23%] | ||
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