Phase 3
N=127
A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT01200758 ↗Enrolled (actual)
127
Serious AEs
36.9%
Results posted
Aug 2015
Primary outcome: Primary: Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab — 83.1; 134.6 micrograms per milliliter (mcg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Rituximab SC (Drug); Rituximab IV (Drug); Cyclophosphamide (Drug); Doxorubicin (Drug); Vincristine (Drug); Prednisone/Prednisolone (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jun 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab |
83.1; 134.6 | — |
| PRIMARY Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL) |
85.1; 80.3 | 0.2835 |
| SECONDARY Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL |
82.8; 90.5 | 0.2047 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL |
84.9; 84.4 | 0.8911 |
| SECONDARY Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL |
25.0; 42.9 | 0.0335 sig |
| SECONDARY Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL |
34.8; 28.2 | 0.2331 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL |
31.7; 32.2 | 0.9157 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL |
57.9; 50.6 | 0.1715 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL |
78.1; 77.9 | 0.9671 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death |
34.6; 31.7 | — |
| SECONDARY Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL |
NA; NA | 0.5526 |
| SECONDARY Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL |
36.1; 35.1 | — |
| SECONDARY Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL |
NA; NA | 0.9115 |
| SECONDARY Percentage of Participants Who Died |
12.7; 8.8 | — |
| SECONDARY Overall Survival (OS) |
NA; NA | — |
| SECONDARY Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab |
2734.21; 3778.93 | — |
| SECONDARY Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab |
250.63; 236.82 | — |
| SECONDARY Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle |
14.00; 12.88; 30.13; 40.00; 45.25; 63.83 | — |
| SECONDARY Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle |
37.69; 61.31; 30.35; 49.47; 28.44; 47.27 | — |
| SECONDARY Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration |
15.60; 22.35; 2.89; 5.19; 1.08; 2.02 | — |
| SECONDARY Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase |
51.6; 54.8; 95.1; 95.0; 99.4; 99.4 | — |
| SECONDARY Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase |
99.4; 100.0; 99.4; 100.0; 99.4; 100.0 | — |
| SECONDARY Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab |
5.8; 2.6; 1.5; 2.0 | — |
| SECONDARY Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab |
10.3; 11.2; 7.6; 13.2 | — |
| SECONDARY Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20 |
11; 20; 35; 18; 16; 13 | — |
| SECONDARY Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion |
81; 13; 2; 4; 0; 88 | — |
Summary
This two-stage, multi-center, randomized, controlled, open-label study will investigate the pharmacokinetics, efficacy and safety of rituximab SC versus rituximab IV in participants with previously untreated follicular non-Hodgkin's lymphoma. Participants will be randomized to receive 375 milligrams per meter square (mg/m^2) rituximab as IV infusion or 1400 milligrams (mg) rituximab SC. In addition, participants will receive standard chemotherapy. Participants who achieved a complete or partial response (PR) after 8 treatment cycles, will receive maintenance treatment for a further maximum number of 12 cycles. Maintenance treatment cycles will be repeated every 8 weeks. This is a two-stage study. Stage 1 was designed to confirm the chosen rituximab SC dose resulting in comparable rituximab serum Ctrough levels compared with rituximab IV, when given as part of induction treatment every 3 weeks. Enrollment for Stage 2 started after the rituximab SC dose was established in Stage 1. Stage 2 aimed to further investigate the efficacy and safety of rituximab SC compared with rituximab IV. The anticipated time on study treatment is 96 weeks.
Eligibility Criteria
Inclusion Criteria
- Cluster of differentiation 20 (CD20)-positive, follicular Non-Hodgkin's lymphoma grade 1, 2, 3a. A tumor biopsy must have been performed within 6 months before study entry with material available for central review
- No prior treatment
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Exclusion Criteria
- Grade 3b follicular lymphoma
- Transformation to high-grade lymphoma secondary to follicular lymphoma
- Types of Non-Hodgkin's lymphoma other than follicular lymphoma
- Presence or history of central nervous system (CNS) disease
- Corticoid therapy during the last 4 weeks, except prednisone treatment less than (<) 20 milligrams per day (mg per day)
- Known active bacterial, viral, fungal, or mycobacterial, or any major episode of infections requiring hospitalization or treatment with IV antibiotics within 4 weeks of start of study medication, or oral antibiotics within 2 weeks prior to start of study medication
Data sourced from ClinicalTrials.gov (NCT01200758). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.