A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma

Phase 3

Completed

Conditions: Lymphoma, Large B-Cell, Diffuse

Interventions: Drug: CHOP
Drug: rituximab [MabThera/Rituxan]

Registration Number: NCT01649856

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This multicenter, randomized, open label parallel-group study will evaluate the efficacy and safety of subcutaneous versus intravenous MabThera/Rituxan (rituximab) in combination with CHOP chemotherapy in patients with previously untreated CD20-positive diffuse large B-Cell lymphoma. Patients will be randomized to receive either MabThera/Rituxan 1400 mg subcutaneously or MabThera/Rituxan 375 mg/m2 intravenously on Day 1 of each cycle for 8 cycles, in combination with 6-8 cycles of CHOP chemotherapy. Anticipated time on study treatment is 6 months.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 572

Inclusion Criteria

Adult patients, >/= 18 and </= 80 years of age at time of study inclusion
Histologically confirmed, previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) according to the WHO classification system
Patients with an International Prognostic Index (IPI) score 1-5, or IPI score 0 with bulky disease, defined as one lesion >/= 7.5 cm
At least one bi-dimensionally measurable lesion defined as >/= 1.5 cm in its largest dimension on CT scan, PET-CT scan or MRI
Adequate hematologic function
Eastern Cooperative Oncology Group (EOCD) performance status </= 2

Exclusion Criteria

Primary or secondary central nervous system lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis
Transformed lymphoma or follicular lymphoma IIIB
Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin, carcinoma in situ of the cervix, or a malignancy that has been treated without curative intent and has been in remission without treatment for >/= 5 years prior to enrolment
Inadequate renal or hepatic function
Known human immunodeficiency virus (HIV) infection or HIV seropositive status
Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with occult or prior HBV infection as defined by protocol may be included. Patients positive for HCV antibody are eligible only if polymerase chain reaction testing for HCV ribonucleic acid is negative.
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
Prior treatment with cytotoxic drugs or rituximab for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody
Pregnant or lactating women

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: Rituximab SC	CHOP	-
A: Rituximab SC	rituximab [MabThera/Rituxan]	-
B: Rituximab IV	CHOP	-
B: Rituximab IV	rituximab [MabThera/Rituxan]	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Response (CR) or Complete Response Unconfirmed (CRu)	Up to approximately 4.25 years	Tumor response was assessed per criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by greater than (\>) 75 percent (%) but still \>1.5 centimeters (cm) in size, and indeterminate bone marrow assessment. The percentage of participants with either response at the end of induction (EOI) was determined with corresponding 95% Pearson-Clopper confidence interval (CI).

Secondary Outcome Measures

Name	Time	Method
Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores	At Cycle 7 (each cycle was 14 or 21 days)	The CTSQ is a validated 16-item questionnaire that measures three domains related to satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)	Hospital time was defined as the amount of time the participant was in the hospital for the course of one cycle of rituximab + CHOP chemotherapy. Where the hospital time was not documented for a given cycle, it was reported as "Missing".
Number of Participants With Relapse or Death at the Time of Primary Analysis	Up to approximately 2 years (assessed at Baseline, Day 1 of each cycle [maximum 8 cycles; each cycle was 14 or 21 days], every 3 months thereafter, and/or 4 weeks after early termination)	Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu. The number of participants who had experienced relapse or death prior to the clinical cut-off date (October 2014) was determined.
Number of Deaths	Up to approximately 4.25 years
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores	At Cycle 7 (each cycle was 14 or 21 days)	The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Median Duration of Rituximab Administration for Each Treatment Cycle	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)	Duration of rituximab administration was defined as the time from start to end of the SC injection or IV infusion. The median duration was reported.
Number of Participants With an Event-Free Survival (EFS) Event	Up to approximately 4.25 years	EFS events included disease progression, relapse, initiation of other anti-lymphoma therapy, or death. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as greater than or equal to (≥) 50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)	Chair time was defined as the amount of time the participant occupied an infusion chair/bed for a single treatment cycle of rituximab + CHOP chemotherapy. Where the chair time was not documented for a given cycle, it was reported as "Missing".
Duration of EFS	Up to approximately 4.25 years	EFS was defined as the time from randomization to first occurrence of disease progression, relapse, initiation of other anti-lymphoma therapy, or death, whichever occurred first. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as a ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.
Duration of Disease-Free Survival (DFS)	Up to approximately 4.25 years	DFS was defined as the time from date of initial CR/CRu to the date of relapse or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.
Number of Participants With Progression, Relapse, or Death	Up to approximately 4.25 years	Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.
Duration of Progression-Free Survival (PFS)	Up to approximately 4.25 years	PFS was defined as the time from randomization to first occurrence of disease progression, relapse, or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.
Duration of Overall Survival (OS)	Up to approximately 4.25 years	OS was defined as the time from randomization to death from any cause.

Trial Locations

Locations (186): EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward
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Blida, Algeria
Centre hospitalo-univerisitaire de Tizi Ouzou - Nedir Mohamed;Service d'hématologie
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Tizi Ouzou, Algeria
Cemic; Haematology
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Buenos Aires, Argentina
Hospital Privado de Comunidad; Oncology
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Mar Del Plata, Argentina
Onze Lieve Vrouwziekenhuis Aalst
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Aalst, Belgium
ZNA Middelheim
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Antwerpen, Belgium
CHU Brugmann (Victor Horta)
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Bruxelles, Belgium
Clin Univ de Bxl Hôpital Erasme
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Bruxelles, Belgium
CHU Charleroi-ISPPC-Espace Santé
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Charleroi, Belgium
CHU de Charleroi
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Charleroi, Belgium
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EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward
🇩🇿Blida, Algeria