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NCT01987505

MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma

Completed Phase 3 Results posted Last updated 26 December 2018
What this trial tests

Phase 3 trial testing Rituximab in Lymphoma, Non Hodgkin in 140 participants. Completed in 11 April 2017.

Timeline
11 November 2013
Primary endpoint
11 April 2017
11 April 2017

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment140
Start date11 November 2013
Primary completion11 April 2017
Estimated completion11 April 2017
Sites39 locations across Spain

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 80, any sex, with Lymphoma, Non Hodgkin. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Administration-Associated Reactions (AARs) Primary · From start of treatment to end of treatment (up to 32 months)

AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab SC 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.

At Least One AAR
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)34.5
Follicular Lymphoma (FL)52.3
Subcutaneous Rituximab48.6
At Least One AAR Grade ≥ 3
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)0
Follicular Lymphoma (FL)2.7
Subcutaneous Rituximab2.1
At Least One Serious AARs
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)0
Follicular Lymphoma (FL)1.8
Subcutaneous Rituximab1.4
Generalised or Remote from the Injection Site AARs
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)57.9
Follicular Lymphoma (FL)11.1
Subcutaneous Rituximab15.1
Localised at the injection site AARs
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)42.1
Follicular Lymphoma (FL)88.9
Subcutaneous Rituximab84.9
Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs) Secondary · From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be 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 worsen during a study are also considered as adverse events. Grading was completed according to the

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)48.3
Follicular Lymphoma (FL)36.0
Subcutaneous Rituximab38.6
Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs) Secondary · From start of treatment to end of treatment (up to 32 months)

Grading of IIRRs was completed according to the CTCAE, version 4.0.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)0.0
Follicular Lymphoma (FL)2.7
Subcutaneous Rituximab2.1
Percentage of Participants With At Least One Serious Adverse Event (SAE) Secondary · From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 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.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)37.9
Follicular Lymphoma (FL)27.9
Subcutaneous Rituximab30.0
Event-Free Survival (EFS) Secondary · From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

EFS was defined as the time from first dose of rituximab IV to first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first. PD: \>/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)25.7920.800 – 30.776
Follicular Lymphoma (FL)54.3951.416 – 57.362
Subcutaneous Rituximab52.31449.162 – 55.466
Progression-Free Survival (PFS) Secondary · From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

PFS was defined as the time from first dose of rituximab IV to the first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or death from any cause. PD: \>/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)27.95223.443 – 32.460
Follicular Lymphoma (FL)54.38951.416 – 57.362
Subcutaneous Rituximab53.11850.108 – 56.127
Overall Survival (OS) Secondary · From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

OS was defined as the time from first dose of rituximab IV to death from any cause.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)37.4233.354 – 41.485
Follicular Lymphoma (FL)60.6159.692 – 61.535
Subcutaneous Rituximab59.51657.999 – 61.033
Disease-Free Survival (DFS) Secondary · From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

DFS was assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus \> 75% decrease in residual lymph node mass, indeterminate bone marrow. Reported here is the truncated mean estimate based on Kaplan-Meier analysis.

GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)26.06223.510 – 28.613
Follicular Lymphoma (FL)NANA – NA
Subcutaneous Rituximab33.04431.489 – 34.600
Treatment Response Rate Secondary · 4-6 weeks after the last dose of Induction (Up to approximately 8 months)

Treatment response rate was classified according to the International Working Group (IWG) response criteria: CR/Cru, partial response (PR), stable disease (SD) and PD. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus \> 75% decrease in residual lymph node mass, indeterminate bone marrow; PR: \>/= 50% decrease lymph nodes and nodal mass size; decrease in liver/spleen size, no new sites; SD: less than a PR, but is not PD; PD: \>/= 50% increase

Complete Response (CR)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)62.1
Follicular Lymphoma (FL)66.7
Subcutaneous Rituximab64.3
Complete Response Unconfirmed (CRU)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)3.4
Follicular Lymphoma (FL)7.4
Subcutaneous Rituximab5.4
Partial Response (PR)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)3.4
Follicular Lymphoma (FL)11.1
Subcutaneous Rituximab7.1
Stable Disease (SD)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)0.0
Follicular Lymphoma (FL)3.7
Subcutaneous Rituximab1.8
Progressive disease (PD)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)17.2
Follicular Lymphoma (FL)7.4
Subcutaneous Rituximab12.5
Unable to Assess (UA)
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)6.9
Follicular Lymphoma (FL)0.0
Subcutaneous Rituximab3.6
Not Evaluable
GroupValue95% CI
Diffuse Large B-Cell Lymphoma (DLBCL)6.9
Follicular Lymphoma (FL)3.7
Subcutaneous Rituximab5.4

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Subcutaneous Rituximab
Serious: 42/140 (30%)
Deaths: 4/140

Serious adverse events (40 terms)

ReactionSystemSubcutaneous Rituximab
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Respiratory tract infectionInfections and infestations
GastroenteritisInfections and infestations
Abdominal painGastrointestinal disorders
Pneumonia pneumococcalInfections and infestations
UrosepsisInfections and infestations
AgranulocytosisBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
VertigoEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
EnteritisGastrointestinal disorders
Gastrointestinal disorderGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Paraesthesia oralGastrointestinal disorders
Umbilical herniaGastrointestinal disorders
PyrexiaGeneral disorders
Enterobacter bacteraemiaInfections and infestations
CellulitisInfections and infestations
Escherichia bacteraemiaInfections and infestations
InfluenzaInfections and infestations
Lung infectionInfections and infestations
SepsisInfections and infestations
Other adverse events (22 terms — click to expand)

ReactionSystemSubcutaneous Rituximab
ErythemaSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
NeutropeniaBlood and lymphatic system disorders
Respiratory tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
Viral upper respiratory tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
ParaesthesiaNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Injection site erythemaGeneral disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
HeadacheNervous system disorders
PainGeneral disorders
Productive coughRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders
DizzinessNervous system disorders

Most-reported serious reactions: Febrile neutropenia, Neutropenia, Pneumonia, Respiratory tract infection, Gastroenteritis, Abdominal pain, Pneumonia pneumococcal, Urosepsis.

Data from ClinicalTrials.gov NCT01987505 adverse events section.

Sponsor's own description

This open-label, single-arm, phase IIIb study will evaluate the safety of switching from intravenous (IV) to subcutaneous (SC) administration of rituximab during first-line treatment for participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have already received at least one full dose of rituximab IV. Participants with FL will be given 1400 mg rituximab SC during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). 1400 mg SC of rituximab will be given to participants with DLBCL once monthly for 4-7 cycles. Treatment duration is expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development.
    Davies A, Berge C, Boehnke A, Dadabhoy A, et al · · 2017 · cited 38× · PMID 28983819 · DOI 10.1007/s12325-017-0610-z
  2. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma.
    Coleman M, Lammers PE, Ciceri F, Jacobs IA. · · 2016 · cited 22× · PMID 26906106 · DOI 10.1016/j.clml.2016.01.004
  3. Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study.
    García-Muñoz R, Quero C, Pérez-Persona E, Domingo-García A, et al · · 2020 · cited 10× · PMID 31573078 · DOI 10.1111/bjh.16227
  4. Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study.
    Petrini M, Gaidano G, Mengarelli A, Consoli U, et al · · 2022 · cited 3× · PMID 35126524 · DOI 10.1155/2022/5581772

Verify or expand the search:

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01987505.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing