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)
- Conditions
- Lymphoma
- Interventions
- Registration Number
- NCT01889069
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rituximab Rituximab 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. Rituximab Vincristine 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. Rituximab Doxorubicin 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. Rituximab Cyclophosphamide 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. Rituximab Prednisone 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. Rituximab Bendamustine 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Administration-Associated Reactions (AAR) Baseline up to 54 months 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
Name Time Method Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months) 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.
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 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 Trough Concentrations of Rituximab 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 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.
Percentage of Participants With Overall Survival (OS) Day 1 until death (up to maximum 54 months) OS was defined as the time from first dose of rituximab to death from any cause.
FL: Plasma Trough Concentrations of Rituximab Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 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 Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 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.
Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs) Baseline up to 54 months Grading of IIRRs was completed according to the CTCAE, version 4.0.
Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria 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) 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 At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) Baseline up to 54 months 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 Treatment-Emergent Serious Adverse Events Baseline up to 54 months 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 Complete Response (CR) According to IWG Response Criteria At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months) 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.
DLBCL: Plasma Concentrations of Rituximab 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 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.
Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria 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) 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.
DLBCL: Apparent Total Clearance (CL/F) of Rituximab 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 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 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 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 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 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 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 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 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 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.
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) 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 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 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) 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.
Trial Locations
- Locations (39)
Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
🇮🇹Mantova, Lombardia, Italy
Seconda università degli studi di napoli; Medicina clinica e sperimentale magrassi - lanzara
🇮🇹Napoli, Campania, Italy
ASST DI CREMA; U O Oncologia Medica
🇮🇹Crema, Lombardia, Italy
Asl ce - p.o. Avers; Uoc ematologia
🇮🇹Aversa, Campania, Italy
Azienda Ospedaliera S. Giovanni Addolorata; UOC Ematologia
🇮🇹Roma, Lazio, Italy
Az. Osp. Papardo; Struttura Complessa Di Ematologia
🇮🇹Messina, Sicilia, Italy
Osp. San Francesco; Ematologia e CTMO
🇮🇹Nuoro, Sardegna, Italy
Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia
🇮🇹Ascoli Piceno, Marche, Italy
Irccs Policlinico San Matteo; Divisione Di Ematologia
🇮🇹Pavia, Lombardia, Italy
Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
🇮🇹Novara, Piemonte, Italy
ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica
🇮🇹Palermo, Sicilia, Italy
Ospedale Santa Chiara; Unita Operativa Di Ematologia
🇮🇹Pisa, Toscana, Italy
Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia
🇮🇹Campobasso, Molise, Italy
A.O. Santa Maria Terni; S.C. Oncoematologia
🇮🇹Terni, Umbria, Italy
Azienda Ospedaliera S.G. Moscati; Divisione Ematologia
🇮🇹Avellino, Campania, Italy
Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
🇮🇹Como, Lombardia, Italy
ASST DI LECCO; Oncologia Medica
🇮🇹Lecco, Lombardia, Italy
Osp. San Raffaele; Dip. Di Oncoematologia
🇮🇹Milano, Lombardia, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
🇮🇹Rozzano, Lombardia, Italy
A.O. San Sebastiano; U.O.C. Oncologia
🇮🇹Caserta, Campania, Italy
Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
🇮🇹Milano, Lombardia, Italy
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
🇮🇹Alessandria, Piemonte, Italy
Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
🇮🇹Bari, Puglia, Italy
Azienda ospedaliera oo rr di foggi; Hematology
🇮🇹Foggia, Puglia, Italy
Ospedale Roberto Binaghi; Centro trapianti di midollo osseo
🇮🇹Cagliari, Sardegna, Italy
ARNAS Garibaldi; Ematologia
🇮🇹Catania, Sicilia, Italy
Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
🇮🇹Palermo, Sicilia, Italy
USL 4 di Prato - Nuovo Ospeale di Prato
🇮🇹Prato, Toscana, Italy
Irccs Crob
🇮🇹Rionero in Vulture, Basilicata, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli; Unità Operativa di Ematologia
🇮🇹Reggio Calabria, Calabria, Italy
Ospedale di Macerata; Medicina Generale
🇮🇹Macerata, Marche, Italy
Ospedale S. Eugenio; Divisione Di Ematologia
🇮🇹Roma, Lazio, Italy
Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
🇮🇹Roma, Lazio, Italy
Osp. Santa Maria Goretti; Ematologia
🇮🇹Latina, Lazio, Italy
Regina Elena National Cancer Institute; Hematology
🇮🇹Roma, Lazio, Italy
ASL Viterbo; Presidio Ospedaliero di Ronciglione; UOC Ematologia
🇮🇹Ronciglione, Lazio, Italy
Ospedale di Civitanova Marche; Medicina Interna
🇮🇹Civitanova Marche, Marche, Italy
Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
🇮🇹Roma, Lazio, Italy
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
🇮🇹Padova, Veneto, Italy