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NCT04660799

A Study on Pharmacokinetics (PK), Efficacy and Safety of Subcutaneous (SC) Versus Intravenous (IV) Rituximab, in Combination With CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) in Previously Untreated Participants With CD20 Positive Diffuse Large B-Cell Lymphoma (DLBCL)

Completed Phase 2 Results posted Last updated 12 October 2023
What this trial tests

Phase 2 trial testing Rituximab IV in Lymphoma, Large B-Cell, Diffuse in 50 participants. Completed in 11 October 2022.

Timeline
24 February 2021
Primary endpoint
23 May 2022
11 October 2022

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment50
Start date24 February 2021
Primary completion23 May 2022
Estimated completion11 October 2022
Sites8 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 80, any sex, with Lymphoma, Large B-Cell, Diffuse. 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.

Subcutaneous Serum Rituximab Trough Concentration (Ctrough SC) and Intravenous Serum Rituximab Trough Concentration (Ctrough IV) Primary · At Cycle 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

For this pharmacokinetics (PK) primary outcome measure the serum rituximab Ctrough for SC and IV administrations were measured at Cycle 7, 21 days after study treatment administration for Cycle 7 (pre-dose of Cycle 8). Geometric mean ratio and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline and are reported in the statistical analysis.

GroupValue95% CI
Rituximab IV+CHOP90.7± 21.1
Rituximab SC+CHOP137.4± 36.3
Observed SC and IV Rituximab Area Under the Curve (AUCsc and AUCiv) Secondary · During Cycle 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

The area under the curve (AUC) for serum rituximab concentration versus time after dosage was measured for SC and IV administrations during Cycle 7. Geometric mean ratio and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline and are reported in the statistical analysis.

GroupValue95% CI
Rituximab IV+CHOP3050.7± 17.8
Rituximab SC+CHOP3806.7± 27.2
Maximum Observed Serum Concentration (Cmax) of Rituximab Secondary · At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks
Cycle 2
GroupValue95% CI
Rituximab IV+CHOP200± 18.3
Rituximab SC+CHOP144± 29.6
Cycle 7
GroupValue95% CI
Rituximab IV+CHOP255± 14.6
Rituximab SC+CHOP228± 28.3
Time to Cmax (Tmax) of Rituximab Secondary · At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks
Cycle 2
GroupValue95% CI
Rituximab IV+CHOP0.140.09 – 0.94
Rituximab SC+CHOP5.421.88 – 13.90
Cycle 7
GroupValue95% CI
Rituximab IV+CHOP0.160.10 – 1.03
Rituximab SC+CHOP1.991.84 – 6.91
Trough Serum Concentration (Ctrough) of Rituximab Secondary · At Cycles 2 and 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

Ctrough was measured at Cycle 2 and Cycle 7, 21 days after study treatment administration for each cycle (pre-dose of Cycle 3 and Cycle 8, respectively).

Cycle 2
GroupValue95% CI
Rituximab IV+CHOP43.2± 26.5
Rituximab SC+CHOP63.5± 36.9
Cycle 7
GroupValue95% CI
Rituximab IV+CHOP90.7± 21.1
Rituximab SC+CHOP137± 36.3
Area Under the Curve (AUC) of Rituximab Secondary · During Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

AUC is the area under the serum concentration curve over the dosing interval of 21 days during Cycle 2 and Cycle 7.

Cycle 2
GroupValue95% CI
Rituximab IV+CHOP1730± 21.5
Rituximab SC+CHOP2130± 31.1
Cycle 7
GroupValue95% CI
Rituximab IV+CHOP3050± 17.8
Rituximab SC+CHOP3810± 27.2
Complete Response Rate (CRR) as Determined by the Independent Review Committee (IRC) Using Lugano Response Criteria (LRC) for Malignant Lymphoma Secondary · 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Per LRC, CR based on positron emission tomography- computed tomography (PET-CT) was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Per LRC, CR based on CT was defined as complete radiologic response i

GroupValue95% CI
Rituximab IV+CHOP62.540.59 – 81.20
Rituximab SC+CHOP80.860.65 – 93.45
Objective Response Rate (ORR), Complete Response (CR) or Partial Response (PR), as Determined by Investigator and IRC Using Lugano Response Criteria (LRC) for Malignant Lymphoma Secondary · 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

ORR=CR+PR. Per LRC: CR by PET-CT: complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass; no new lesions, no FDG-avid disease in bone marrow; CR by CT: complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi, no extralymphatic disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow; PR by PET-CT: partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseli

Investigator
GroupValue95% CI
Rituximab IV+CHOP70.848.91 – 87.38
Rituximab SC+CHOP88.569.85 – 97.55
IRC
GroupValue95% CI
Rituximab IV+CHOP66.744.68 – 84.37
Rituximab SC+CHOP80.860.65 – 93.45
CRR, as Determined by IRC Using International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) 1999 Guidelines Secondary · 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

CRR was assessed according to the IWG Response Criteria for NHL 1999 guidelines and included CR and CR unconfirmed (CRu). CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by \> 75 % but still \>1.5 cm in size, and indeterminate bone marrow assessment.

GroupValue95% CI
Rituximab IV+CHOP58.336.64 – 77.89
Rituximab SC+CHOP65.444.33 – 82.79
CRR, as Determined by the Investigator Using Lugano Response Criteria for Malignant Lymphoma Secondary · 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Per LRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses reg

GroupValue95% CI
Rituximab IV+CHOP58.336.64 – 77.89
Rituximab SC+CHOP76.956.35 – 91.03
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · AEs were reported up to 28 days after the last dose (up to approximately 7 months), and SAEs were reported up to 6 months after the last dose of study treatment (up to approximately 1 year)

AE: any untoward medical occurrence in a subject administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. New disease, exacerbation of existing disease, recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test associated with symptoms or leading to a change in study/concomitant treatment or discontinuation from stu

AEs
GroupValue95% CI
Rituximab IV+CHOP24
Rituximab SC+CHOP26
SAEs
GroupValue95% CI
Rituximab IV+CHOP11
Rituximab SC+CHOP8
Number of Participants With Rituximab Administration-related Reactions (ARRs) Secondary · Up to 24 hours after the last dose of study treatment (up to approximately 24 weeks)

Adverse events occurring within 24 hours after administration of rituximab (rituximab IV or rituximab SC) and considered related to the study drug, were considered as ARRs. ARRs could present with one or more of the following symptoms: allergic reaction, arthralgia, bronchospasm, chills, cough, dizziness, dyspnoea, headache, hypertension, hypotension, myalgia, nausea, pruritus, pyrexia, rash, tachycardia, urticaria, vomiting.

GroupValue95% CI
Rituximab IV+CHOP6
Rituximab SC+CHOP7

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious adverse events (NSAEs) were reported up to 28 days after the last dose (up to approximately 7 months). Serious adverse events (SAEs) and adverse events of special interest (AESIs) were reported up to 6 months after the last dose of study treatment (up to approximately 1 year). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rituximab IV+CHOP
Serious: 11/24 (46%)
Deaths: 2/24
Rituximab SC+CHOP
Serious: 8/26 (31%)
Deaths: 1/26

Serious adverse events (20 terms)

ReactionSystemRituximab IV+CHOPRituximab SC+CHOP
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
MyelosuppressionBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
NauseaGastrointestinal disorders
Multiple organ dysfunction syndromeGeneral disorders
Pneumocystis jirovecii pneumoniaInfections and infestations
SepsisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Accidental overdoseInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
DizzinessNervous system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Skin toxicitySkin and subcutaneous tissue disorders
Other adverse events (49 terms — click to expand)

ReactionSystemRituximab IV+CHOPRituximab SC+CHOP
AnaemiaBlood and lymphatic system disorders
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
Neutrophil count increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypoaesthesiaNervous system disorders
NauseaGastrointestinal disorders
Weight decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
LeukocytosisBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Gamma-glutamyltransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HyperuricaemiaMetabolism and nutrition disorders
Pigmentation disorderSkin and subcutaneous tissue disorders
Infusion site reactionGeneral disorders
PneumoniaInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Injection related reactionInjury, poisoning and procedural complications
White blood cell count increasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
HypertensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
TachycardiaCardiac disorders
Abdominal distensionGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Neutrophil count decreased, Platelet count decreased, White blood cell count decreased, Myelosuppression, Cardiac arrest, Nausea.

Data from ClinicalTrials.gov NCT04660799 adverse events section.

Sponsor's own description

This is a multicenter China-only study to investigate the PK, efficacy and safety of SC rituximab versus IV rituximab, both in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in previously untreated participants with CD20 positive DLBCL. Participants will be randomized to receive eight cycles of rituximab SC or rituximab IV combined with six or eight cycles of standard CHOP chemotherapy. After the end of study treatment, participants will be followed-up every 3 months for 6 months.

Publications & conference data

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

  1. Pharmacokinetics, efficacy, and safety of subcutaneous versus intravenous rituximab in previously untreated Chinese patients with CD20+ diffuse large B-cell lymphoma: a phase II randomized controlled trial.
    Gao Y, Zhang L, Gao S, Yang Y, et al · · 2025 · cited 1× · PMID 39773004 · DOI 10.1080/10428194.2024.2439525
  2. PB2307: PHARMACOKINETICS, EFFICACY AND SAFETY OF SUBCUTANEOUS VERSUS INTRAVENOUS RITUXIMAB COMBINED WITH CHOP IN CHINESE PATIENTS WITH UNTREATED CD20-POSITIVE DIFFUSE LARGE B CELL LYMPHOMA: A RANDOMIZED TRIAL
    Gao Y, Zhang L, Gao S, Yang Y, et al · · 2023

Verify or expand the search:

Other trials of Rituximab IV

Trials testing the same drug.

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Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

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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/NCT04660799.

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