A Randomized, Open-label, Mutli-centre Study to Evaluate Patient Preference With Subcutaneous Administration of Rituximab Versus Intravenous Rituximab in Previously Untreated Patients With CD20+ Diffuse Large B-cell Lymphoma or CD20+ Follicular Non-Hodgkin's Lymphoma Grades 1, 2, OR 3A
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 743
- Primary Endpoint
- Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6
Overview
Brief Summary
This multi-center, open-label, randomized study will evaluate the participant preference with subcutaneous versus intravenous administration of MabThera/Rituxan (rituximab) in participants with CD20+ diffuse large B-cell lymphoma or CD20+ follicular non-Hodgkin's lymphoma. In Arm A, participants will receive MabThera/Rituxan 375 mg/m2 intravenously (IV) on Day 1 of Cycle 1 and MabThera/Rituxan 1400 mg subcutaneously (SC) on Day 1 of Cycles 2-4, followed by MabThera/Rituxan IV in Cycles 5-8. Participants in Arm B will receive MabThera/Rituxan IV in Cycles 1-4 and SC in Cycles 5-8. All participants will receive 6-8 cycles of standard chemotherapy (according to local country practice) with 8 cycles of MabThera/Rituxan. Anticipated time on study treatment is up to 24 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult participants , \>/= 18 and \</= 80 years of age
- •Histologically confirmed, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2, or 3a, according to World Health Organization (WHO) classification
- •An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion \>/= 7.5 cm, or Follicular Lymphoma International Prognostic Index (FLIPI; low, intermediate or high risk)
- •At least one bi-dimensionally measurable lesion defined as \>/=1.5 cm in its largest dimension on CT scan
- •Eastern Cooperative Oncology Group (ECOG) performance status \</= 3
Exclusion Criteria
- •Transformed lymphoma or follicular lymphoma IIIB
- •Primary central nervous system (CNS) lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis
- •History of other malignancy that could affect compliance with the protocol or interpretation of the results; this includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission for \>/= 5 years prior to enrolment; participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible
- •Prior therapy for DLBCL or NHL, with the exception of nodal biopsy or local irradiation
- •Prior treatment with cytotoxic drugs (with the exclusion of intrathecal methotrexate for CNS prophylaxis in DLBCL) or rituximab for another condition, or prior use of an anti-CD20 drug
- •Prior use of monoclonal antibody within 3 months prior to randomization
- •Chemotherapy or other investigational therapy within 28 days prior to randomization
- •Ongoing corticosteroid use \> 30 mg/day prednisolone or equivalent
- •Inadequate renal. hematologic or hepatic function
- •Active and/or severe infection or any major episode of infection within 4 weeks prior to randomization
Arms & Interventions
Arm A
Participants in Arm A received one cycle of rituximab 375 mg/m^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone/Prednisolone (CHOP) (Drug)
Arm A
Participants in Arm A received one cycle of rituximab 375 mg/m^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Cyclophosphamide, Vincristine, Prednisone/Prednisolone (CVP) (Drug)
Arm A
Participants in Arm A received one cycle of rituximab 375 mg/m^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Bendamustine (Drug)
Arm A
Participants in Arm A received one cycle of rituximab 375 mg/m^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Rituximab (Drug)
Arm B
Participants in Arm B received four cycles of rituximab 375 mg/m^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone/Prednisolone (CHOP) (Drug)
Arm B
Participants in Arm B received four cycles of rituximab 375 mg/m^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Cyclophosphamide, Vincristine, Prednisone/Prednisolone (CVP) (Drug)
Arm B
Participants in Arm B received four cycles of rituximab 375 mg/m^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Bendamustine (Drug)
Arm B
Participants in Arm B received four cycles of rituximab 375 mg/m^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Intervention: Rituximab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6
Time Frame: Cycle 6 (Up to 24 weeks)
Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing cycle 6.
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8
Time Frame: Cycle 8 (Up to 32 weeks)
Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing Cycle 8.
Secondary Outcomes
- Cancer Therapy Satisfaction Questionnaire (CTSQ) Score(During Cycle 4, 8 of treatment (Up to 32 weeks))
- Rituximab Administration Satisfaction Questionnaire (RASQ) Score(During Cycle 4, 8 of treatment (Up to 32 weeks))
- Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV])(Cycle 1-4, Cycle 5-8 for both SC and IV (Up to 32 weeks))
- Number of Participants With Treatment Emergent Adverse Events (AEs)(Randomization of first participant to clinical cutoff date (Up to 4 years))
- Overall Survival (OS)(From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years))
- Percentage of Participants With Anti-Rituximab Antibodies Over Time(Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years))
- Complete Response (CR) Rate(28 days (± 3 days) after Day 1 of the last dose of induction treatment)
- Event-free Survival (EFS)(From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years))
- Disease-free Survival (DFS)(From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years))
- Progression-free Survival (PFS)(From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years))
- Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time(Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years))
- Summary of Observed Serum Rituximab Concentration(Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years))