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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01649856
First received: July 23, 2012
Last updated: January 15, 2016
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Lymphoma, Large B-Cell, Diffuse
Drug: CHOP
Drug: rituximab [MabThera/Rituxan]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparative, Randomized, Parallel-group, Multi-center, Phase IIIB Study to Investigate the Efficacy of Subcutaneous (SC) Rituximab Versus Intravenous (IV) Rituximab Both in Combination With CHOP (R-CHOP) in Previously Untreated Patients With CD20-positive Diffuse Large B-cell Lymphoma (DLBCL)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With CR or CRu at the Time of Primary Analysis [ Time Frame: Up to approximately 7 months (assessed at Baseline, Cycle 4, and 30 days after the start of the last rituximab cycle [maximum 8 cycles; each cycle was 14 or 21 days]) ] [ Designated as safety issue: No ]
    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:
  • Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores [ Time Frame: At Cycle 7 (each cycle was 14 or 21 days) ] [ Designated as safety issue: No ]
    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.

  • Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores [ Time Frame: At Cycle 7 (each cycle was 14 or 21 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle [ Time Frame: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days) ] [ Designated as safety issue: No ]
    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".

  • Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle [ Time Frame: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days) ] [ Designated as safety issue: No ]
    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 an Event-Free Survival (EFS) Event at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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. The number of participants with one or more EFS events prior to the clinical cut-off date (October 2014) was determined.

  • Duration of EFS at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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. The duration of EFS was to be determined at the time of clinical cut-off (October 2014) using Kaplan-Meier analysis.

  • Number of Participants With Relapse or Death at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Duration of Disease-Free Survival (DFS) at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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. The duration of DFS was to be determined at the time of clinical cut-off (October 2014) using Kaplan-Meier analysis.

  • Number of Participants With Progression, Relapse, or Death at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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. The number of participants who had experienced progression, relapse, or death prior to the clinical cut-off date (October 2014) was determined.

  • Duration of Progression-Free Survival (PFS) at the Time of Primary Analysis [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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. The duration of PFS was to be determined using Kaplan-Meier analysis.

  • Number of Deaths at the Time of Primary Analysis [ Time Frame: Up to approximately 2 years (survival followed from randomization until death) ] [ Designated as safety issue: No ]
    The number of participants who had experienced death prior to the clinical cut-off date (October 2014) was determined.

  • Duration of Overall Survival (OS) at the Time of Primary Analysis [ Time Frame: Up to approximately 2 years (survival followed from randomization until death) ] [ Designated as safety issue: No ]
    OS was defined as the time from randomization to death from any cause. The duration of OS was to be determined using Kaplan-Meier analysis.


Enrollment: 572
Study Start Date: August 2012
Estimated Study Completion Date: September 2016
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Rituximab SC Drug: CHOP
CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles
Drug: rituximab [MabThera/Rituxan]
The first rituximab dose will be administered intravenously on Day of Cycle 1 at a dose of 375 mg/m2. Subsequent doses of 1400 mg are administered subcutaneously on Day 1 of each cycle, for a further 7 cycles
Active Comparator: B: Rituximab IV Drug: CHOP
CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles
Drug: rituximab [MabThera/Rituxan]
375 mg/m2 intravenously on Day 1 of each cycle, 8 cycles

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01649856

  Show 183 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01649856     History of Changes
Other Study ID Numbers: MO28107  2012-000669-19 
Study First Received: July 23, 2012
Results First Received: January 15, 2016
Last Updated: January 15, 2016
Health Authority: Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA)

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 28, 2016