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)

NCT04660799 | Completed Phase 2 Results FDA Drug

• 1 other identifier: YO42207
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

Mabthera, Rituximab, SC, Subcutaneous, DLBCL

Outcome Measures

Primary Outcomes (1)

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

  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.

  At Cycle 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

Secondary Outcomes (13)

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

  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

• Maximum Observed Serum Concentration (Cmax) of Rituximab

  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

• Time to Cmax (Tmax) of Rituximab

  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

• Trough Serum Concentration (Ctrough) of Rituximab

  At Cycles 2 and 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

• Area Under the Curve (AUC) of Rituximab

  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

Study Arms (2)

Rituximab IV+CHOP

ACTIVE COMPARATOR

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

Drug: Rituximab IV; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Paracetamol; Drug: Diphenhydramine hydrochloride or alternative antihistamine

Rituximab SC+CHOP

EXPERIMENTAL

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.

Drug: Rituximab SC; Drug: Rituximab IV; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Paracetamol; Drug: Diphenhydramine hydrochloride or alternative antihistamine

Interventions

Rituximab IV DRUG

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

Also known as: MabThera

Rituximab IV+CHOP

Rituximab SC DRUG

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

Also known as: MabThera

Rituximab SC+CHOP

Cyclophosphamide DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Doxorubicin DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Vincristine DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Prednisone DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Paracetamol DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Diphenhydramine hydrochloride or alternative antihistamine DRUG

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

Rituximab IV+CHOP; Rituximab SC+CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL)
• Participants with an International Prognostic Index (IPI) score of 1 to 5 or IPI score of 0 with bulky disease, defined as one lesion \>/=7.5 cm
• At least one bi-dimensionally measurable lesion defined as \>/=1.5 cm in its largest dimension on CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Left ventricular ejection fraction (LVEF) \>/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram
• A negative serum pregnancy test or a negative urine pregnancy test within 7 days prior to study treatment
• For men who are not surgically sterile, agreement to use a barrier method of contraception during the treatment period and until \>/=12 months after the last dose of rituximab SC or rituximab IV or according to institutional guidelines for CHOP chemotherapy, whichever is longer, and agreement to request that their partners use an additional method of contraception
• For women of reproductive potential who are not surgically sterile, agreement to use adequate methods of contraception during the treatment period and until \>/=12 months after the last dose of rituximab SC or rituximab IV or according to institutional guidelines for CHOP chemotherapy, whichever is longer
• Adequate hematologic function confirmed within 14 days prior to randomization

You may not qualify if:

• Transformed non-Hodgkin's lymphoma (NHL) or types of NHL other than DLBCL and its subtypes according to World Health Organization classification
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
• Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation or surgery for diagnosis
• Prior treatment with cytotoxic drugs or rituximab for another condition (e.g.,rheumatoid arthritis) or prior use of an anti-CD20 antibody
• Current or recent treatment with another investigational drug or participation in another investigational therapeutic study
• Ongoing corticosteroid use (\>30 mg/day of prednisone or equivalent)
• Primary CNS lymphoma, blastic variant of mantle cell lymphoma, or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, and primary cutaneous DLBCL
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Evidence of significant, uncontrolled concomitant diseases including but not limited to significant cardiovascular disease or pulmonary disease
• Any of the following abnormal laboratory values: creatinine \>1.5 upper limit of normal (ULN), aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \>2.5ULN, total bilirubin \>1.5ULN, prothrombin time - international normalized ratio (PT-INR) / partial thromboplastin time (PTT) / activated partial thromboplastin time (aPTT)\>1.5ULN
• Positive test results for chronic hepatitis B (HBV) and or hepatitis C (HCV) infection; Participants with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody \[HBcAb\]) may be included if HBV DNA is undetectable; Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• Known history of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Peking University Third Hospital

Beijing, 100191, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Fujian Provincial Cancer Hospital

Fuzhou, 350014, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, 330019, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjing, 300060, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, 710061, China

Location

Related Publications (1)

• Gao Y, Zhang L, Gao S, Yang Y, Zhang Q, Zhang H, He P, Li F, Jing H, Grange S, Bu L, Wang Q, Li L, Huang H. 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. Leuk Lymphoma. 2025 Apr;66(4):680-690. doi: 10.1080/10428194.2024.2439525. Epub 2025 Jan 7.

  PMID: 39773004 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Acetaminophen; Diphenhydramine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 9, 2020
• Study Start: February 24, 2021
• Primary Completion: May 23, 2022
• Study Completion: October 11, 2022
• Last Updated: October 12, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (8)