A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT01200758
• Recruitment Status: Completed
• First Posted: September 14, 2010
• Results First Posted: August 5, 2015
• Last Update Posted: November 27, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This two-stage, multi-center, randomized, controlled, open-label study will investigate the pharmacokinetics, efficacy and safety of rituximab SC versus rituximab IV in participants with previously untreated follicular non-Hodgkin's lymphoma. Participants will be randomized to receive 375 milligrams per meter square (mg/m^2) rituximab as IV infusion or 1400 milligrams (mg) rituximab SC. In addition, participants will receive standard chemotherapy. Participants who achieved a complete or partial response (PR) after 8 treatment cycles, will receive maintenance treatment for a further maximum number of 12 cycles. Maintenance treatment cycles will be repeated every 8 weeks. This is a two-stage study. Stage 1 was designed to confirm the chosen rituximab SC dose resulting in comparable rituximab serum Ctrough levels compared with rituximab IV, when given as part of induction treatment every 3 weeks. Enrollment for Stage 2 started after the rituximab SC dose was established in Stage 1. Stage 2 aimed to further investigate the efficacy and safety of rituximab SC compared with rituximab IV. The anticipated time on study treatment is 96 weeks.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Rituximab SC; Drug: Rituximab IV; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone/Prednisolone	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 410 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Two-Stage Phase III, International, Multi-Center, Randomized, Controlled, Open-Label Study to Investigate the Pharmacokinetics, Efficacy and Safety of Rituximab SC in Combination With CHOP or CVP Versus Rituximab IV in Combination With CHOP or CVP in Patients With Previously Untreated Follicular Lymphoma Followed by Maintenance Treatment With Either Rituximab SC or Rituximab IV
• Actual Study Start Date: February 15, 2011
• Actual Primary Completion Date: June 12, 2012
• Actual Study Completion Date: October 31, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP); Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	Drug: Rituximab IV; Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.; Other Name: MabThera; Drug: Cyclophosphamide; Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks.; Drug: Doxorubicin; Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks.; Drug: Vincristine; Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks.; Drug: Prednisone/Prednisolone; Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.
Experimental: Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP); First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.	Drug: Rituximab SC; First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.; Other Name: MabThera; Drug: Cyclophosphamide; Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks.; Drug: Doxorubicin; Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks.; Drug: Vincristine; Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks.; Drug: Prednisone/Prednisolone; Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.

Outcome Measures

Primary Outcome Measures :

1. Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab [ Time Frame: Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks) ]
2. Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL) [ Time Frame: Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (≥) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.

Secondary Outcome Measures :

1. Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Overall Response comprised CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in the SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
2. Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Overall Response comprised of CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumour response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
3. Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Complete Response was comprised CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
4. Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
5. Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks) ]
   Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
6. Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks) ]
   Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
7. Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks) ]
   Overall Response comprised of CR, CRu, or PR . A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
8. Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death [ Time Frame: Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description) ]
   Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
9. Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description) ]
   PFS was defined as the time from randomization to disease progression/relapse or death due to any cause. If the specified event (disease progression/relapse, death) did not occur, PFS was censored at the last tumor assessment date showing no disease progression, either during treatment or follow-up. Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. PFS analysis was performed using Kaplan - Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
10. Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description) ]
    Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
11. Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL [ Time Frame: Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description) ]
    Event-free survival was defined as the time from randomization to disease progression/relapse, death or initiation of new NHL therapy. If the specified event (progression/relapse, death or new anti-lymphoma treatment) did not occur, event-free survival was censored at the last tumor assessment date either during treatment or follow up. Event-free survival analysis was performed using Kaplan-Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
12. Percentage of Participants Who Died [ Time Frame: Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years]) ]
13. Overall Survival (OS) [ Time Frame: Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years]) ]
    OS was defined as the time from randomization to death due to any cause. Participants without event were censored at the time of last follow-up information for survival, ie, at the last time known to be alive.
14. Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab [ Time Frame: Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description) ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Predose (within 2 hr) and 24 hrs postdose on Cy 7 (D1,3,7,15), predose (0 hr) on Cy 8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy 7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
15. Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab [ Time Frame: Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description) ]
    Predose (within 2 hr) and 24 hrs postdose on Cy7 (D1,3,7,15), predose (0 hr) on Cy8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
16. Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle [ Time Frame: Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description) ]
    Stage I and II (Induction): Rituximab IV: Predose (within 2 hr) on D1 of Cy1-8 (1 Cy=3 weeks & 4 weeks for Cy8); Rituximab SC: Predose (within 2 hr) on D1 of Cy1 & Cy3-8 (1 Cy=3 weeks and 4 weeks for Cy8), predose (within 2 hr) on D0 of Cy2 (up to data cutoff of 31 Oct 2013 [up to 32 months])
17. Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle [ Time Frame: Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description) ]
    Stage I and II (maintenance): D29 of Cy8 (induction; 1 Cy=4 weeks), predose (within 2 hr) on D1 of Cy9 to 19 (maintenance Cy1 to 12 [1 Cy=8 weeks]; up to data cutoff of 11 Jan 2016 [up to 6 years])
18. Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration [ Time Frame: 12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years]) ]
19. Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase [ Time Frame: Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2 ]
    Depletion is defined as a cluster of differentiation (CD) 19 value <80 cells per cubic millimeter (cells/mm^3).
20. Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase [ Time Frame: Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years]) ]
    Depletion is defined as a CD19 value <80 cells/mm^3.
21. Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab [ Time Frame: Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description) ]
    Levels of HACA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
22. Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab [ Time Frame: Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description) ]
    Levels of HAHA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
23. Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20 [ Time Frame: After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20) ]
    All investigator physicians and nurses involved in this study were asked to provide the staff time that could be saved with each administration of rituximab SC as compared with rituximab IV to participants in routine practice afetr Cy 8, 15, 20 and categorized as less than (<) 1 hr, at least 1 hr but <2 hrs, at least 2 hrs but <3 hrs, at least 3 hrs but <4 hrs, >/=4 hrs. Staff were asked not to consider the time needed for the first IV administration. Analysis was done in all participants to show a comparison on the time saved by staffs when administered via SC and IV.
24. Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion [ Time Frame: After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20) ]
    All investigator physicians and nurses involved in this study were asked to complete question i.e. "Which formulation of rituximab (SC or IV) do you think is more convenient?" based on their experience with the rituximab SC and IV formulations across all participants and presented as rituximab SC is much more convenient; rituximab SC is a little more convenient; both formulations are equally convenient; rituximab IV is a little more convenient; and rituximab IV is much more convenient.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Cluster of differentiation 20 (CD20)-positive, follicular Non-Hodgkin's lymphoma grade 1, 2, 3a. A tumor biopsy must have been performed within 6 months before study entry with material available for central review
• No prior treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

• Grade 3b follicular lymphoma
• Transformation to high-grade lymphoma secondary to follicular lymphoma
• Types of Non-Hodgkin's lymphoma other than follicular lymphoma
• Presence or history of central nervous system (CNS) disease
• Corticoid therapy during the last 4 weeks, except prednisone treatment less than (<) 20 milligrams per day (mg per day)
• Known active bacterial, viral, fungal, or mycobacterial, or any major episode of infections requiring hospitalization or treatment with IV antibiotics within 4 weeks of start of study medication, or oral antibiotics within 2 weeks prior to start of study medication

Contacts and Locations

Locations

Australia, New South Wales

Gosford Hospital; Cancer Care Services

Gosford, New South Wales, Australia, 2250

Wollongong Hospital; Cancer Services

Wollongong, New South Wales, Australia, 2500

Australia, Queensland

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia, 4029

Gold Coast Hospital; Haematology Department

Southport, Queensland, Australia, 4215

Australia, South Australia

Queen Elizabeth Hospital; Haematology

Woodville South, South Australia, Australia, 5011

Belgium

UZ Antwerpen

Edegem, Belgium, 2650

CHU Sart-Tilman

Liège, Belgium, 4000

Sint Augustinus Wilrijk

Wilrijk, Belgium, 2610

Bosnia and Herzegovina

University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept

Banja Luka, Bosnia and Herzegovina, 88000

University Clinical Center Sarajevo, Clinic for Hematology

Sarajevo, Bosnia and Herzegovina, 71000

University Clinical Centre Tuzla, Clinic for Oncology, Hematology and Radiotherapy

Tuzla, Bosnia and Herzegovina, 75000

Brazil

Nucleo de Hematologia e Transplante de Medula Ossea de Minas Gerais

Belo Horizonte, MG, Brazil, 30140-001

Hospital das Clinicas - UFRGS

Porto Alegre, RS, Brazil, 90035-003

Hospital Sao Lucas - PUCRS

Porto Alegre, RS, Brazil, 90610-000

Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia

Sao Paulo, SP, Brazil, 01221-020

Hospital das Clinicas - FMUSP

Sao Paulo, SP, Brazil, 05403-000

Bulgaria

UMHAT Dr Georgi Stranski; Hematology

Pleven, Bulgaria, 5800

Umhat S. George; Hematology

Plovdiv, Bulgaria, 4002

Specialised Hospital For Treatment Of Hematological Diseases; Hematology

Sofia, Bulgaria, 1756

Mhat Sveta Marina; Dept. of Haematology

Varna, Bulgaria, 9010

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Quebec

Cite de La Sante de Laval; Hemato-Oncologie

Laval, Quebec, Canada, H7M 3L9

Centre de sante et de services sociaux Rimouski Neigette

Rimouski, Quebec, Canada, G5L 5T1

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada, J1H 5N4

Centre hospitalier regional de Trois-Rivieres

Trois-Rivieres, Quebec, Canada, G8Z 3R9

Canada

CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie

Quebec, Canada, G1J 1Z4

Colombia

Fundacion Cardioinfantil

Bogota, Colombia

Centro Medico Imbanaco

Cali, Colombia

Hospital Pablo Tobon Uribe

Medellin-Antioquia, Colombia

Oncólogos de Occidente

Pereira, Colombia, 600004

Croatia

UHC Rijeka

Rijeka, Croatia, 51000

University Hospital Center Zagreb; Haematology Department

Zagreb, Croatia, 10000

Denmark

Herlev Uni Hospital; Hæmatologisk Afdeling L 121

Herlev, Denmark, 2730

Rigshospitalet; Hæmatologisk Klinik

København Ø, Denmark, 2100

Odense Universitetshospital; Hæmatologisk Afdeling

Odense C, Denmark, 5000

Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium

Roskilde, Denmark, 4000

Vejle Hospital; Dept of Medicine, Division of Hematology

Vejle, Denmark, 7100

Aarhus Universitetshospital, Hæmatologisk Afdeling R

Århus, Denmark, 8000

Finland

Helsinki University Central Hospital; Dept of Oncology

Helsinki, Finland, 00029

France

Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie

Bordeaux, France, 33077

Hopital Henri Mondor; Hematologie Clinique

Creteil, France, 94010

Chu Site Du Bocage;Hematologie Clinique

Dijon, France, 21079

Clinique Victor Hugo; Chimiotherapie

Le Mans, France, 72015

Institut J Paolii Calmettes; Onco Hematologie 1

Marseille, France, 13273

Hopital Saint Eloi; Hematologie Oncologie Medicale

Montpellier, France, 34295

Hopital Hotel Dieu Et Hme;Hopital De Jour

Nantes, France, 44093

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

Paris, France, 75475

Hopital De Haut Leveque; Hematologie Clinique

Pessac, France, 33604

Ch Lyon Sud; Hemato Secteur Jules Courmont

Pierre Benite, France, 69495

Hopital De La Miletrie; Hematologie Et Oncologie Medicale

Poitiers, France, 86021

Hopital Bretonneau; Hematologie Therapie Cellulaire

Tours, France, 37044

Georgia

M.Zodelava's Hematology Center

Tbilisi, Georgia, 0112

Mediclub

Tbilisi, Georgia, 0160

Institute of Hematology and Transfusiology

Tbilisi, Georgia, 0177

Chemotherapy and Immunotherapy Clinic Medulla

Tbilisi, Georgia, 0186

Germany

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, Germany, 10707

Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie

Darmstadt, Germany, 64283

Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin

Dresden, Germany, 01307

PIOH PD Dr. R. Schnell - Dr. H. Schulz - Dr. M. Hellmann

Frechen, Germany, 50226

Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I

Giessen, Germany, 35392

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik

Greifswald, Germany, 17475

Internistisch-Onkologische Gemeinschaftspraxis; Dres. Rohrberg, Hurtz, Schma usw.

Halle, Germany, 06110

Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hannover, Germany, 30625

St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2

Karlsruhe, Germany, 76137

UKSH Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie

Kiel, Germany, 24105

Gemeinschaftspraxis PD Dr. med. Marcel Reiser und Dr. med. Ildiko Kátay

Koeln, Germany, 50674

Onkologische Gemeinschaftspraxis

Magdeburg, Germany, 39104

Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach

Marburg, Germany, 35037

Medizinisches Versorgungszentrum MOP

München, Germany, 80335

Praxis Dr.med. Jens Uhlig

Naunhof, Germany, 04683

Praxis Dr. Clemens Müller-Naendrup (Onkologische Schwerpunktpraxis im MVZ 2 GmbH)

Olpe, Germany, 57462

Prosper-Hospital, Medizinische Klinik I

Recklinghausen, Germany, 45659

Praxis Dr. Fenchel

Saalfeld, Germany, 07318

Caritas Kilinik St. Theresia; Abt. Innere Medizin

Saarbruecken, Germany, 66113

Praxis für Hämatologie & Onkologie

Saarbruecken, Germany, 66113

Greece

Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine

Athens, Greece, 115 27

Attiko Hospital; Haematology Clinic

Athens, Greece, 124 62

Italy

Azienda Ospedaliera Ospedale S.Carlo; Ematologia

Potenza, Basilicata, Italy, 85100

A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica

Napoli, Campania, Italy, 80131

AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia

Reggio Emilia, Emilia-Romagna, Italy, 42100

Ospedale S. Eugenio; Divisione Di Ematologia

Roma, Lazio, Italy, 00144

Uni Degli Studi Di Genova; 1A Divisione Di Ematologia

Genova, Liguria, Italy, 16132

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia

Brescia, Lombardia, Italy, 25123

Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia

Milano, Lombardia, Italy, 20141

IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo

San Giovanni Rotondo, Puglia, Italy, 71013

Ospedale Ca Foncello; Ematologia

Treviso, Veneto, Italy, 31100

Ospedale Di Vicenza; Nefrologia, Ematologia

Vicenza, Veneto, Italy, 36100

Macedonia, The Former Yugoslav Republic of

University Clinic for Hematology; HSCT Department

Skopje, Macedonia, The Former Yugoslav Republic of, 1000

University Clinic of Hematology Skopje, Hospital Care Department

Skopje, Macedonia, The Former Yugoslav Republic of, 1000

Malaysia

University Malaya Medical Center; Hematology Unit of Department of Internal Medicine

Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia, 59100

Ampang Hospital; Department of Haematology

Ampang, Malaysia, 68000

Sarawak General Hospital; Department of Radiotherapy, Oncology and Palliative care

Sarawak, Malaysia, 93586

Mexico

Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre

Chihuahua, Mexico, 31000

Hospital General De Culiacan; Servicio De Hematologia

Culiacan, Mexico, 80230

Hospital Universitario Dr. Jose E. Gonzalez; Haematology

Monterrey, Mexico, 64460

Centro de Estudios Clinicos de Queretaro (CECLIQ)

Queretaro, Mexico, 76000

New Zealand

Canterbury Health Laboratories; Haematology

Christchurch, New Zealand, 8011

Palmerston North Hospital; Regional Cancer Treatment Service

Palmerston North, New Zealand, 4442

Peru

Instituto;Oncologico Miraflores

Lima, Peru, 18

Oncosalud Sac; Oncología

Lima, Peru, 41

Hospital Maria Auxiliadora

Lima, Peru, Lima 29

Romania

Spitalul Clinic Judetean de Urgenta Brasov,Clinica de Hematologie

Brasov, Romania, 500326

Fundeni Clinical Inst. ; Hematology Dept

Bucharest, Romania, 022328

Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi, Clinica de Hematologie

Iasi, Romania, 700111

Institutul Regional de Oncologie Iasi; Clinica de Hematologie

Iasi, Romania, 700483

Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie

Targu-mures, Romania, 540136

Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie

Timisoara, Romania, 300079

Russian Federation

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan, Russian Federation, 420029

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis

Moscow, Russian Federation, 115478

Haematology Research Center; Haematology

Moscow, Russian Federation, 125167

Penza Regional Oncology Dispensary

Penza, Russian Federation, 440071

St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

Saint-Petersburg, Russian Federation, 197022

Research Inst. of Hematology & Blood Transfusion ; Hematology

St Petersburg, Russian Federation, 191024

Russian Scientific Center of Radiology and Surgical Technologies; Dept of Radiology

St.Petersburg, Pesochny, Russian Federation, 197758

Serbia

Institute of Hematology

Belgrade, Serbia, 11000

Clinical Center Vojvodine; Clinic for Hematology

Novi Sad, Serbia, 21000

Singapore

National University Hospital; National University Cancer Institute, Singapore (NCIS)

Singapore, Singapore, 119228

Singapore General Hospital; Department of Haematology

Singapore, Singapore, 169608

National Cancer Centre; Medical Oncology

Singapore, Singapore, 169610

Slovakia

St. Elisabeths Cancer Center

Bratislava, Slovakia, 812 50

National Cancer Inst. ; Dept. of Chemotherapy

Bratislava, Slovakia, 833 10

South Africa

National Hospital; Oncotherapy Dept

Bloemfontein, South Africa, 9301

King Edward VIII; Department of Haematology

Congella, South Africa, 4013

Durban Oncology Center

Durban, South Africa, 4091

University of Witwatersrand/Johannesburg Hospital; Dept. of ocnology

Johannesburg, South Africa, 2193

Cancercare

Kraaifontein, South Africa, 7570

Spain

Hospital Universitario Puerta del Mar; Servicio de Hematologia

Cádiz, Cadiz, Spain, 11009

Hospital del Mar; Servicio de Hematologia

Barcelona, Spain, 08003

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, Spain, 08035

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Spain, 08036

Hospital Duran i Reynals; Servicio de Hematologia

Barcelona, Spain, 08907

Hospital Universitario de la Princesa; Servicio de Hematologia

Madrid, Spain, 28006

Hospital Ramon y Cajal; Servicio de Hematologia

Madrid, Spain, 28034

Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia

Murcia, Spain, 30120

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Sevilla, Spain, 41013

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, Spain, 46026

Thailand

National Cancer Inst.

Bangkok, Thailand, 10400

Siriraj Hospital; Division of Hematology, Department of Medicine

Bangkok, Thailand, 10700

Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine

Khon Kaen, Thailand, 40002

Turkey

Adana Baskent University Hospital; Medical Oncology

Adana, Turkey, 01120

Istanbul University Cerrahpasa Medical Faculty; Hematology Department

Istanbul, Turkey, 34098

Bilim University School of Medicine; Hematology

Istanbul, Turkey, 34394

Dokuz Eylul Uni ; Hematology

Izmir, Turkey, 35100

Ege Uni Medical School; Hematology

Izmir, Turkey, 35100

United Kingdom

Ninewells Hospital & Medical School; Ward 34

Dundee, United Kingdom, DD1 9SY

Maidstone & Tonbridge Wells Hospital; Kent Oncology Center

Maidstone, United Kingdom, ME16 9QQ

Derriford Hospital; Department of Haematology

Plymouth, United Kingdom, PL6 8DH

Queen's Hospital; Oncology

Romford, United Kingdom, RM7 0AG

Southampton General Hospital

Southampton, United Kingdom, SO16 6YD

Pinderfields General Hospital; Dept of Haematology

Wakefield, United Kingdom, WF1 4DG

New Cross Hospital; Dept. Of Haematology

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Davies A, Merli F, Mihaljevic B, Mercadal S, Siritanaratkul N, Solal-Celigny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. doi: 10.1016/S2352-3026(17)30078-9. Epub 2017 May 2.

Davies A, Merli F, Mihaljevic B, Siritanaratkul N, Solal-Celigny P, Barrett M, Berge C, Bittner B, Boehnke A, McIntyre C, Macdonald D. Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study. Lancet Oncol. 2014 Mar;15(3):343-52. doi: 10.1016/S1470-2045(14)70005-1. Epub 2014 Feb 10.

Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.

Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013 Sep 17;109(6):1556-61. doi: 10.1038/bjc.2013.371. Epub 2013 Sep 3.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01200758
• Other Study ID Numbers: BO22334; 2010-021377-36
• First Posted: September 14, 2010
• Results First Posted: August 5, 2015
• Last Update Posted: November 27, 2018
• Last Verified: October 2018

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Prednisone; Prednisolone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Glucocorticoids