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)

NCT ID: NCT04660799

Last Updated: 2023-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-24
• Study Completion Date: 2022-10-11

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab IV+CHOP

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

Group Type: ACTIVE_COMPARATOR

Rituximab IV

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Paracetamol

Intervention Type: DRUG

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

Diphenhydramine hydrochloride or alternative antihistamine

Intervention Type: 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 SC+CHOP

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.

Group Type: EXPERIMENTAL

Rituximab SC

Intervention Type: DRUG

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

Rituximab IV

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Paracetamol

Intervention Type: DRUG

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

Diphenhydramine hydrochloride or alternative antihistamine

Intervention Type: 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

Interventions

Rituximab IV

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

Intervention Type: DRUG

Rituximab SC

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

Intervention Type: DRUG

Rituximab IV

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Paracetamol

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

Intervention Type: DRUG

Diphenhydramine hydrochloride or alternative antihistamine

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

Intervention Type: DRUG

Other Intervention Names

MabThera; MabThera; MabThera

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Peking University Third Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

Fujian Provincial Cancer Hospital

Fuzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, , China

Tianjin Medical University Cancer Institute & Hospital

Tianjing, , China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 39773004 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

YO42207

Identifier Type: -

Identifier Source: org_study_id