Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Histamine Antagonists

Histamine H1 Antagonists

Diphenhydramine

Promethazine

Histamine

Histamine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Neurotransmitter Agents

Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.

Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.

Rituximab will be administered intravenously through Cycle 1-8 at a standard dose of 375 mg/m\^2 (milligram per square meter).

Rituximab IV

Rituximab will be administered subcutaneously through Cycle 2-8 at a dose of 1400 milligram (mg).

Rituximab SC

Rituximab will be administered intravenously in Cycle 1 at a standard dose of 375 mg/m\^2.

Cyclophosphamide will be administered IV at a dose of 750 mg/m\^2

Doxorubicin will be administered IV at a dose of 50 mg/m\^2

Vincristine will be administered IV at a dose of 1.4 mg/m\^2

Prednisone will be administered orally at a dose of 100 mg/day

All participants are required to receive 1000 mg oral paracetamol as premedication prior to starting each infusion of rituximab

Paracetamol

All participants are required to receive 50-100 mg oral diphenhydramine hydrochloride or alternative antihistamine as premedication prior to starting each infusion of rituximab

Diphenhydramine hydrochloride or alternative antihistamine

Clinical Trials

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.

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)

A Phase II Comparative, Open-Label, Randomized, Multicenter, China-Only Study to Investigate the Pharmacokinetics, Efficacy and Safety of Subcutaneous Rituximab Versus Intravenous Rituximab Both in Combination With CHOP in Previously Untreated Patients With CD20 Positive Diffuse Large B Cell Lymphoma

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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.

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.

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).

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

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 in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative.

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 baseline + residual masses of any size; no new lesions, residual uptake higher than in normal bone marrow but reduced compared with baseline; PR by CT: ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion absent/normal, regressed, but no increase; spleen regressed by \>50 % in length beyond normal; no new lesions.

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.

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 regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative.

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 study drug as well as events related to protocol-mandated interventions are considered AEs. SAEs: any event that met any of these criteria: fatal, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, medically significant or required intervention to prevent any of the outcomes listed here.

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.

Reported here is the number of participants who had a positive ADA assay result at baseline or post-baseline. The post-baseline results are divided in treatment-enhanced ADAs and treatment-induced ADAs. Treatment-enhanced ADAs are participants with a positive ADA result at baseline who had one or more post-baseline titer results that was at least 0.60 titer unit greater than the baseline titer result. Treatment-induced ADAs include participants with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result.

Reported here is the number of participants who had a positive anti-rHuPH20 antibody assay result at baseline or post-baseline. The post-baseline results are divided in treatment-enhanced anti-rHuPH20 antibodies and treatment-induced anti-rHuPH20 antibodies. Treatment-enhanced anti-rHuPH20 antibodies are participants with a positive anti-rHuPH20 antibody result at baseline who had one or more post-baseline titer results that was at least 0.60 titer unit greater than the baseline titer result. Treatment-induced anti-rHuPH20 antibodies include participants with negative or missing baseline anti-rHuPH20 antibody result(s) and at least one positive post-baseline anti-rHuPH20 antibody result.

Hoffmann-La Roche

The safety analysis population consisted of all randomized participants who received at least one dose of study drug, with participants grouped according to treatment received.

Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.

Rituximab IV+CHOP

Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.

Rituximab SC+CHOP

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Communications

Geometric mean ratio of Ctrough SC/Ctrough IV and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline.

The Per Protocol PK population included all enrolled participants who adhered to the protocol and were assigned to arms as treated. Exclusions were made for the following reasons: missing Ctrough Cycle 7 sample, Cycle 7 Ctrough sample collected with more than 3 days deviation from planned date on Day 22, given a dose that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), a Cycle 7 dose delay of more than 7 days, an assay error impacting Cycle 7 Ctrough measurement.

Subcutaneous Serum Rituximab Trough Concentration (Ctrough SC) and Intravenous Serum Rituximab Trough Concentration (Ctrough IV)

Geometric mean ratio of AUCsc/AUCiv and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline.

Observed SC and IV Rituximab Area Under the Curve (AUCsc and AUCiv)

Cycle 2

Cycle 7

PK analyses were based on all participants with at least one PK assessment. PK analyses were analyzed as treated. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete, where the PK analysis might be influenced.

Maximum Observed Serum Concentration (Cmax) of Rituximab

Time to Cmax (Tmax) of Rituximab

Trough Serum Concentration (Ctrough) of Rituximab

Area Under the Curve (AUC) of Rituximab

Stratified by IPI score: IPI 0-2 = low to low-intermediate risk versus IPI 3-5 = high-intermediate to high risk

The intent-to-treat (ITT) population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

Complete Response Rate (CRR) as Determined by the Independent Review Committee (IRC) Using Lugano Response Criteria (LRC) for Malignant Lymphoma

Investigator; Stratified by IPI score: IPI 0-2 = low to low-intermediate risk versus IPI 3-5 = high-intermediate to high risk

IRC; Stratified by IPI score: IPI 0-2 = low to low-intermediate risk versus IPI 3-5 = high-intermediate to high risk

Investigator

The ITT population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

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

CRR, as Determined by IRC Using International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) 1999 Guidelines

CRR, as Determined by the Investigator Using Lugano Response Criteria for Malignant Lymphoma

SAEs

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of Participants With Rituximab Administration-related Reactions (ARRs)

Baseline

Post-baseline: Treatment-enhanced

Post-baseline: Treatment-induced

The immunogenicity analysis population consisted of all participants with at least one anti-drug antibody (ADA) assessment. Participants were grouped according to treatment received or, if no treatment was received prior to study discontinuation, according to treatment assigned.

Number of Participants Positive for Anti-drug Antibodies (ADAs) to Rituximab

The immunogenicity analysis population consisted of all participants with at least one anti-rHuPH20 assessment. Participants were grouped according to treatment received or, if no treatment was received prior to study discontinuation, according to treatment assigned.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial