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.
|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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