Back to resultsA Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Rituximab
Cyclophosphamide
Vincristine
Doxorubicin
Prednisone
Bendamustine
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed, CD20+ DLBCL or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2 or 3a, according to the World Health Organization (WHO) classification system
- Currently being treated with rituximab intravenously (IV) in the Induction or Maintenance period, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 milligrams per square-meter (mg/m^2) administered without interruption or early discontinuation (i.e. tolerability issues)
- Expectation and current ability for the participant to receive at least 4 additional cycles of treatment during the Induction period or 6 additional cycles of treatment during the Maintenance period (participants with follicular NHL)
- An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion greater than or equal to (>=) 7.5 centimeters (cm), or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) assessed before the first rituximab IV administration in Induction period
- At least one bi-dimensionally measurable lesion defined as >=1.5 cm in its largest dimension on computed tomography (CT) scan
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 3
Exclusion Criteria:
- Transformed lymphoma or FL IIIB
- Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL
- History of other malignancy
- Ongoing corticosteroid use greater than (>) 30 milligrams per day (mg/day) of prednisone or equivalent
- Inadequate renal, hematologic, or hepatic function
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Contraindications to any of the individual components of standard chemotherapy
- Other serious underlying medical conditions, which, in the Investigator's judgement, could impair the ability of the participant to participate in the study
- Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis)
- Active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or human immunodeficiency virus (HIV) infection
Sites / Locations
- Irccs Crob
- Azienda Ospedaliera Bianchi-Melacrino-Morelli; Unità Operativa di Ematologia
- Azienda Ospedaliera S.G. Moscati; Divisione Ematologia
- Asl ce - p.o. Avers; Uoc ematologia
- A.O. San Sebastiano; U.O.C. Oncologia
- Seconda università degli studi di napoli; Medicina clinica e sperimentale magrassi - lanzara
- Osp. Santa Maria Goretti; Ematologia
- Ospedale S. Eugenio; Divisione Di Ematologia
- Regina Elena National Cancer Institute; Hematology
- Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
- Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
- Azienda Ospedaliera S. Giovanni Addolorata; UOC Ematologia
- ASL Viterbo; Presidio Ospedaliero di Ronciglione; UOC Ematologia
- Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
- ASST DI CREMA; U O Oncologia Medica
- ASST DI LECCO; Oncologia Medica
- Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
- Osp. San Raffaele; Dip. Di Oncoematologia
- Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
- Irccs Policlinico San Matteo; Divisione Di Ematologia
- Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
- Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia
- Ospedale di Civitanova Marche; Medicina Interna
- Ospedale di Macerata; Medicina Generale
- Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia
- Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
- Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
- Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
- Azienda ospedaliera oo rr di foggi; Hematology
- Ospedale Roberto Binaghi; Centro trapianti di midollo osseo
- Osp. San Francesco; Ematologia e CTMO
- ARNAS Garibaldi; Ematologia
- Az. Osp. Papardo; Struttura Complessa Di Ematologia
- ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica
- Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
- Ospedale Santa Chiara; Unita Operativa Di Ematologia
- USL 4 di Prato - Nuovo Ospeale di Prato
- A.O. Santa Maria Terni; S.C. Oncoematologia
- IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab
Arm Description
Participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Outcomes
Primary Outcome Measures
Percentage of Participants With Administration-Associated Reactions (AAR)
AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Secondary Outcome Measures
Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.
Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs)
Grading of IIRRs was completed according to the CTCAE, version 4.0.
Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events
SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria
EFS was defined as the time from first dose of rituximab to first occurrence of progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurred first.
Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria
PFS was defined as the time from first dose of rituximab to the first occurrence of disease progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or death from any cause, whichever occurred first.
Percentage of Participants With Overall Survival (OS)
OS was defined as the time from first dose of rituximab to death from any cause.
Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria
DFS assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occured first.
Percentage of Participants With Complete Response (CR) According to IWG Response Criteria
Complete response required: 1) the complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities, 2) all lymph nodes and nodal masses had regressed to normal size, 3) the spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and not be palpable on physical examination and 4) if the bone marrow was involved by lymphoma before treatment, the infiltrate was cleared on repeat bone marrow aspirate and biopsy of the same site. CR/unconfirmed (CRu) included those patients who fulfilled criteria 1 and 3 above as well as 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that regressed by more than 75% in the SPD and 2) indeterminate bone marrow. Response was assessed according to the IWG response criteria.
FL: Plasma Trough Concentrations of Rituximab
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Pharmacokinetic (PK) data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
DLBCL: Plasma Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Plasma Trough Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Apparent Total Clearance (CL/F) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21
Plasma concentrations of rituximab in participants with DLBCL by chemotherapy regimen cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 14 days (R-CHOP-14) or cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 21 days (R-CHOP-21) in the PK) population.DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores
Patient-assessed satisfaction was evaluated using RASQ. Participants were asked questions regarding convenience and satisfaction for rituximab SC. 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. DLBCL participants could be enrolled at cycle 2, cycle 3, or cycle 4. FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must be able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Each Cycle is 21 days for DLBCL. Each Cycle 21 days during the Induction phase and 2 months during Maintenance phase for FL.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01889069
Brief Title
A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
Official Title
A Single Arm, Multicentre, Phase IIIB Study to Evaluate Safety, Efficacy and Pharmacokinetic (PK) of Subcutaneous (SC) Rituximab Administered During Induction Phase or Maintenance in Previously Untreated Patients With CD20+ Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
July 31, 2013 (Actual)
Primary Completion Date
May 28, 2019 (Actual)
Study Completion Date
May 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This single arm, multicenter study will evaluate the safety, efficacy and pharmacokinetic (PK) of subcutaneous (SC) rituximab in previously untreated participants with cluster of differentiation 20 positive (CD20+) DLBCL or FL. In addition to standard chemotherapy, participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
159 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera, Rituxan
Intervention Description
Rituximab will be administered at a dose of 1400 mg SC once a month for at least 4 doses during the Induction period, and at a dose of 1400 mg SC once every two months for at least 6 doses during the Maintenance period.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be administered as per standard local practice as a part of standard chemotherapy regimen.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Vincristine will be administered as per standard local practice as a part of standard chemotherapy regimen.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Doxorubicin will be administered as per standard local practice as a part of standard chemotherapy regimen.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone will be administered as per standard local practice as a part of standard chemotherapy regimen.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine will be administered as per standard local practice as a part of standard chemotherapy regimen.
Primary Outcome Measure Information:
Title
Percentage of Participants With Administration-Associated Reactions (AAR)
Description
AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Time Frame
Baseline up to 54 months
Secondary Outcome Measure Information:
Title
Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)
Description
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.
Time Frame
Baseline up to 54 months
Title
Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs)
Description
Grading of IIRRs was completed according to the CTCAE, version 4.0.
Time Frame
Baseline up to 54 months
Title
Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events
Description
SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Time Frame
Baseline up to 54 months
Title
Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria
Description
EFS was defined as the time from first dose of rituximab to first occurrence of progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurred first.
Time Frame
Day 1 up to first occurrence of progression or relapse, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first (up to maximum 54 months)
Title
Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria
Description
PFS was defined as the time from first dose of rituximab to the first occurrence of disease progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or death from any cause, whichever occurred first.
Time Frame
Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months)
Title
Percentage of Participants With Overall Survival (OS)
Description
OS was defined as the time from first dose of rituximab to death from any cause.
Time Frame
Day 1 until death (up to maximum 54 months)
Title
Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria
Description
DFS assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occured first.
Time Frame
From 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occurs first (up to maximum 54 months) (end of Induction period = up to 8 months)
Title
Percentage of Participants With Complete Response (CR) According to IWG Response Criteria
Description
Complete response required: 1) the complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities, 2) all lymph nodes and nodal masses had regressed to normal size, 3) the spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and not be palpable on physical examination and 4) if the bone marrow was involved by lymphoma before treatment, the infiltrate was cleared on repeat bone marrow aspirate and biopsy of the same site. CR/unconfirmed (CRu) included those patients who fulfilled criteria 1 and 3 above as well as 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that regressed by more than 75% in the SPD and 2) indeterminate bone marrow. Response was assessed according to the IWG response criteria.
Time Frame
At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months)
Title
FL: Plasma Trough Concentrations of Rituximab
Description
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Pharmacokinetic (PK) data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time Frame
Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Title
FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
Description
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time Frame
Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Title
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
Description
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time Frame
Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Title
DLBCL: Plasma Concentrations of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Plasma Trough Concentrations of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 pre-dose on Day 1
Title
DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Apparent Total Clearance (CL/F) of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
Description
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21
Description
Plasma concentrations of rituximab in participants with DLBCL by chemotherapy regimen cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 14 days (R-CHOP-14) or cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 21 days (R-CHOP-21) in the PK) population.DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time Frame
Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Title
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores
Description
Patient-assessed satisfaction was evaluated using RASQ. Participants were asked questions regarding convenience and satisfaction for rituximab SC. 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. DLBCL participants could be enrolled at cycle 2, cycle 3, or cycle 4. FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must be able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Each Cycle is 21 days for DLBCL. Each Cycle 21 days during the Induction phase and 2 months during Maintenance phase for FL.
Time Frame
DLBCL: Cycle (C) 2, C3, C4, C5, C6, End of C8; FL: Induction: C3, C4, C5, C6, C8, Maintenance: C2, C3, C4, C5, C6, C7, C8, C10, C12, End of treatment (4-8 weeks after last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed, CD20+ DLBCL or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2 or 3a, according to the World Health Organization (WHO) classification system
Currently being treated with rituximab intravenously (IV) in the Induction or Maintenance period, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 milligrams per square-meter (mg/m^2) administered without interruption or early discontinuation (i.e. tolerability issues)
Expectation and current ability for the participant to receive at least 4 additional cycles of treatment during the Induction period or 6 additional cycles of treatment during the Maintenance period (participants with follicular NHL)
An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion greater than or equal to (>=) 7.5 centimeters (cm), or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) assessed before the first rituximab IV administration in Induction period
At least one bi-dimensionally measurable lesion defined as >=1.5 cm in its largest dimension on computed tomography (CT) scan
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 3
Exclusion Criteria:
Transformed lymphoma or FL IIIB
Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL
History of other malignancy
Ongoing corticosteroid use greater than (>) 30 milligrams per day (mg/day) of prednisone or equivalent
Inadequate renal, hematologic, or hepatic function
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
Contraindications to any of the individual components of standard chemotherapy
Other serious underlying medical conditions, which, in the Investigator's judgement, could impair the ability of the participant to participate in the study
Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis)
Active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or human immunodeficiency virus (HIV) infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Irccs Crob
City
Rionero in Vulture
State/Province
Basilicata
ZIP/Postal Code
85028
Country
Italy
Facility Name
Azienda Ospedaliera Bianchi-Melacrino-Morelli; Unità Operativa di Ematologia
City
Reggio Calabria
State/Province
Calabria
ZIP/Postal Code
89100
Country
Italy
Facility Name
Azienda Ospedaliera S.G. Moscati; Divisione Ematologia
City
Avellino
State/Province
Campania
ZIP/Postal Code
83100
Country
Italy
Facility Name
Asl ce - p.o. Avers; Uoc ematologia
City
Aversa
State/Province
Campania
ZIP/Postal Code
81031
Country
Italy
Facility Name
A.O. San Sebastiano; U.O.C. Oncologia
City
Caserta
State/Province
Campania
ZIP/Postal Code
81100
Country
Italy
Facility Name
Seconda università degli studi di napoli; Medicina clinica e sperimentale magrassi - lanzara
City
Napoli
State/Province
Campania
ZIP/Postal Code
80138
Country
Italy
Facility Name
Osp. Santa Maria Goretti; Ematologia
City
Latina
State/Province
Lazio
ZIP/Postal Code
04100
Country
Italy
Facility Name
Ospedale S. Eugenio; Divisione Di Ematologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00144
Country
Italy
Facility Name
Regina Elena National Cancer Institute; Hematology
City
Roma
State/Province
Lazio
ZIP/Postal Code
00144
Country
Italy
Facility Name
Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
City
Roma
State/Province
Lazio
ZIP/Postal Code
00152
Country
Italy
Facility Name
Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
Azienda Ospedaliera S. Giovanni Addolorata; UOC Ematologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00184
Country
Italy
Facility Name
ASL Viterbo; Presidio Ospedaliero di Ronciglione; UOC Ematologia
City
Ronciglione
State/Province
Lazio
ZIP/Postal Code
01037
Country
Italy
Facility Name
Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
City
Como
State/Province
Lombardia
ZIP/Postal Code
22100
Country
Italy
Facility Name
ASST DI CREMA; U O Oncologia Medica
City
Crema
State/Province
Lombardia
ZIP/Postal Code
26013
Country
Italy
Facility Name
ASST DI LECCO; Oncologia Medica
City
Lecco
State/Province
Lombardia
ZIP/Postal Code
23900
Country
Italy
Facility Name
Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
City
Mantova
State/Province
Lombardia
ZIP/Postal Code
46100
Country
Italy
Facility Name
Osp. San Raffaele; Dip. Di Oncoematologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
Irccs Policlinico San Matteo; Divisione Di Ematologia
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
City
Rozzano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
Facility Name
Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia
City
Ascoli Piceno
State/Province
Marche
ZIP/Postal Code
63100
Country
Italy
Facility Name
Ospedale di Civitanova Marche; Medicina Interna
City
Civitanova Marche
State/Province
Marche
ZIP/Postal Code
62012
Country
Italy
Facility Name
Ospedale di Macerata; Medicina Generale
City
Macerata
State/Province
Marche
ZIP/Postal Code
62100
Country
Italy
Facility Name
Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia
City
Campobasso
State/Province
Molise
ZIP/Postal Code
86100
Country
Italy
Facility Name
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
City
Alessandria
State/Province
Piemonte
ZIP/Postal Code
15121
Country
Italy
Facility Name
Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
City
Novara
State/Province
Piemonte
ZIP/Postal Code
28100
Country
Italy
Facility Name
Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
City
Bari
State/Province
Puglia
ZIP/Postal Code
70124
Country
Italy
Facility Name
Azienda ospedaliera oo rr di foggi; Hematology
City
Foggia
State/Province
Puglia
ZIP/Postal Code
71100
Country
Italy
Facility Name
Ospedale Roberto Binaghi; Centro trapianti di midollo osseo
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09126
Country
Italy
Facility Name
Osp. San Francesco; Ematologia e CTMO
City
Nuoro
State/Province
Sardegna
ZIP/Postal Code
08100
Country
Italy
Facility Name
ARNAS Garibaldi; Ematologia
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95122
Country
Italy
Facility Name
Az. Osp. Papardo; Struttura Complessa Di Ematologia
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98165
Country
Italy
Facility Name
ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
Facility Name
Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
Facility Name
Ospedale Santa Chiara; Unita Operativa Di Ematologia
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56100
Country
Italy
Facility Name
USL 4 di Prato - Nuovo Ospeale di Prato
City
Prato
State/Province
Toscana
ZIP/Postal Code
59100
Country
Italy
Facility Name
A.O. Santa Maria Terni; S.C. Oncoematologia
City
Terni
State/Province
Umbria
ZIP/Postal Code
05100
Country
Italy
Facility Name
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
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