Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01889069
Other study ID # ML28881
Secondary ID 2013-000647-12
Status Completed
Phase Phase 3
First received
Last updated
Start date July 31, 2013
Est. completion date May 28, 2019

Study information

Verified date July 2020
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 159
Est. completion date May 28, 2019
Est. primary completion date May 28, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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

Study Design


Intervention

Drug:
Rituximab
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.
Cyclophosphamide
Cyclophosphamide will be administered as per standard local practice as a part of standard chemotherapy regimen.
Vincristine
Vincristine will be administered as per standard local practice as a part of standard chemotherapy regimen.
Doxorubicin
Doxorubicin will be administered as per standard local practice as a part of standard chemotherapy regimen.
Prednisone
Prednisone will be administered as per standard local practice as a part of standard chemotherapy regimen.
Bendamustine
Bendamustine will be administered as per standard local practice as a part of standard chemotherapy regimen.

Locations

Country Name City State
Italy Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia Alessandria Piemonte
Italy Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia Ascoli Piceno Marche
Italy Azienda Ospedaliera S.G. Moscati; Divisione Ematologia Avellino Campania
Italy Asl ce - p.o. Avers; Uoc ematologia Aversa Campania
Italy Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica Bari Puglia
Italy Ospedale Roberto Binaghi; Centro trapianti di midollo osseo Cagliari Sardegna
Italy Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia Campobasso Molise
Italy A.O. San Sebastiano; U.O.C. Oncologia Caserta Campania
Italy ARNAS Garibaldi; Ematologia Catania Sicilia
Italy Ospedale di Civitanova Marche; Medicina Interna Civitanova Marche Marche
Italy Ospedale Valduce;U.O.S. Oncologia Ed Ematologia Como Lombardia
Italy ASST DI CREMA; U O Oncologia Medica Crema Lombardia
Italy Azienda ospedaliera oo rr di foggi; Hematology Foggia Puglia
Italy Osp. Santa Maria Goretti; Ematologia Latina Lazio
Italy ASST DI LECCO; Oncologia Medica Lecco Lombardia
Italy Ospedale di Macerata; Medicina Generale Macerata Marche
Italy Az. Osp. Carlo Poma; Divisione Di Oncologia Medica Mantova Lombardia
Italy Az. Osp. Papardo; Struttura Complessa Di Ematologia Messina Sicilia
Italy Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico Milano Lombardia
Italy Osp. San Raffaele; Dip. Di Oncoematologia Milano Lombardia
Italy Seconda università degli studi di napoli; Medicina clinica e sperimentale magrassi - lanzara Napoli Campania
Italy Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad Novara Piemonte
Italy Osp. San Francesco; Ematologia e CTMO Nuoro Sardegna
Italy IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II Padova Veneto
Italy ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica Palermo Sicilia
Italy Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto Palermo Sicilia
Italy Irccs Policlinico San Matteo; Divisione Di Ematologia Pavia Lombardia
Italy Ospedale Santa Chiara; Unita Operativa Di Ematologia Pisa Toscana
Italy USL 4 di Prato - Nuovo Ospeale di Prato Prato Toscana
Italy Azienda Ospedaliera Bianchi-Melacrino-Morelli; Unità Operativa di Ematologia Reggio Calabria Calabria
Italy Irccs Crob Rionero in Vulture Basilicata
Italy Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo Roma Lazio
Italy Azienda Ospedaliera S. Giovanni Addolorata; UOC Ematologia Roma Lazio
Italy Ospedale S. Eugenio; Divisione Di Ematologia Roma Lazio
Italy Regina Elena National Cancer Institute; Hematology Roma Lazio
Italy Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol Roma Lazio
Italy ASL Viterbo; Presidio Ospedaliero di Ronciglione; UOC Ematologia Ronciglione Lazio
Italy Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia Rozzano Lombardia
Italy A.O. Santa Maria Terni; S.C. Oncoematologia Terni Umbria

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Baseline up to 54 months
Secondary 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. Baseline up to 54 months
Secondary 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. Baseline up to 54 months
Secondary 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. Baseline up to 54 months
Secondary 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. 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)
Secondary 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. Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months)
Secondary Percentage of Participants With Overall Survival (OS) OS was defined as the time from first dose of rituximab to death from any cause. Day 1 until death (up to maximum 54 months)
Secondary 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. 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)
Secondary 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. At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months)
Secondary 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. Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Secondary 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. Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Secondary 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. Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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
Secondary 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. 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)
See also
  Status Clinical Trial Phase
Recruiting NCT05540340 - A Study of Melphalan in People With Lymphoma Getting an Autologous Hematopoietic Cell Transplant Phase 1
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Completed NCT00001512 - Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Completed NCT01410630 - FLT-PET/CT vs FDG-PET/CT for Therapy Monitoring of Diffuse Large B-cell Lymphoma
Active, not recruiting NCT04270266 - Mind-Body Medicine for the Improvement of Quality of Life in Adolescents and Young Adults Coping With Lymphoma N/A
Terminated NCT00801931 - Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders Phase 1/Phase 2
Completed NCT01949883 - A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma Phase 1
Completed NCT01682226 - Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies Phase 2
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT05019976 - Radiation Dose Study for Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma N/A
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Completed NCT04434937 - Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213) Phase 2
Completed NCT01855750 - A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma Phase 3
Terminated NCT00788125 - Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Phase 1/Phase 2
Terminated NCT00775268 - 18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma Phase 1/Phase 2
Active, not recruiting NCT04188678 - Resiliency in Older Adults Undergoing Bone Marrow Transplant N/A
Terminated NCT00014560 - Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia Phase 1
Recruiting NCT04977024 - SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer Phase 2
Active, not recruiting NCT03936465 - Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer Phase 1