Safety Study of Rituximab (SC) Administered in Participants With CD20+ DLBCL or CD20+ Follicular NHL Grade 1 to 3A

An Open-Label, Multinational, Multicenter, Phase IIIB Study to Assess Safety of Rituximab Following Subcutaneous Administration in Patients With CD20+ DLBCL or CD20+ Follicular NHL Grade 1 to 3A

This open-label, single-arm study will evaluate the safety of rituximab subcutaneously (SC) administered during first line treatment for follicular non-Hodgkin's lymphoma (NHL) (Induction and/or Maintenance treatment plus 24 months of follow up), or diffuse large B-cell lymphoma (DLBCL) (treatment plus 24 months of follow-up).

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Fludarabine

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Annaba, Algeria, 23000
    • Hôpital Dorban CHU Annaba, Service d'Hématologie
  • Blida, Algeria, 09000
    • EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward
  • Oran, Algeria, 31000
    • EHU Oran, Service d'Hématologie et de Thérapie Cellulaire
  • Tizi Ouzou, Algeria, 15000
    • Centre hospitalo-univerisitaire de Tizi Ouzou - Nedir Mohamed;Service d'hématologie
• Morocco
  • Casablanca, Morocco, 20100
    • CHU 20 Aout Service D'Onco-Hematologie Pediatrique
  • Casablanca, Morocco, 20340
    • Clinique AlMadina; Service hematologie
  • Marrakech, Morocco, 40000
    • Centre Hospitalier Uni Ire de Marrakech; Oncologie-Hématologie
  • Rabat, Morocco, 10090
    • Hôpital d'enfants de Rabat - Service d'hémato-oncologie pédiatrique
• Tunisia
  • Monastir, Tunisia, 5000
    • CHU Fattouma Bourguiba, Monastir; Service d'hématologie
  • Sfax, Tunisia, 3025
    • CHU Hédi Chacker; Service d'hématologie
  • Sousse, Tunisia, 4000
    • CHU Farhat Hached; Service d'hématologie
  • Tunis, Tunisia, 1008
    • Aziza Othmana Hospital; Clinical Haematology
  • Tunis, Tunisia, 1008
    • Hopital Militaire d'instruction de Tunis; Service d'hématologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed, cluster of differentiation (CD)20+ DLBCL or CD20+ follicular NHL grade 1 to 3a, according to the world health organization (WHO) classification system
• Currently being treated with rituximab IV in the Induction or Maintenance setting, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 milligrams per square meter (mg/m^2) administered without interruption or early discontinuation because of tolerability issues
• Expectation and current ability for the participants to receive at least four additional cycles of treatment during the Induction phase or six additional cycles of treatment during the Maintenance phase (participants with follicular NHL)

Exclusion Criteria:

• Transformed lymphoma or FL IIIB
• History of other malignancy that could affect compliance with the protocol or interpretation of results. This includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for greater than or equal to (>/=) 5 years prior to dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rituximab; Participants with FL and DLBCL will receive rituximab SC 1400 milligrams (mg) once a month for a minimum of 4 cycles as induction therapy. Participants with FL will continue to receive rituximab once in 2 months for a minimum of 6 cycles as maintenance therapy according to local standards of care. Participants will also receive standard chemotherapy regimen (CHOP [cyclophosphamide+doxorubicin+vincristine+prednisone], CVP [cyclophosphamide+vincristine+prednisone] or FC [fludarabine+cyclophosphamide]) during induction.

Drug: Rituximab; Rituximab SC 1400 mg; Other Names: MabThera®; Drug: Cyclophosphamide; Cyclophosphamide will be administered as per standard local practice.; Other Names: Endoxan; Drug: Doxorubicin; Doxorubicin will be administered as per standard local practice.; Drug: Vincristine; Vincristine will be administered as per standard local practice.; Drug: Prednisone; Prednisone will be administered as per standard local practice.; Drug: Fludarabine; Fludarabine will be administered as per standard local practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Administration-Associated Reactions (AARs)	AARs defined as all related adverse events (AEs) occurring within 24 hours of rituximab SC administration, including infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof.	Within 24 hours of each rituximab SC administration (maximum treatment duration up to 32 months for FL participants and up to 8 months for DLBCL participants)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria	EFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to first occurrence of progression or relapse, according to the IWG response criteria or other country standards, or initiation of a non-protocolspecified anti-lymphoma therapy or death, whichever occurs first.	From first dose of rituximab intravenous (IV) and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])
Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria	PFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to the first occurrence of progression or relapse, according to the IWG response criteria (Cheson et al. 1999) or other country standards, or death from any cause.	From first dose of rituximab IV and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])
Overall Survival (OS)	OS is defined as the time from first dose of rirtuximab (analysed using both first dose of IV and first dose of SC) until death from any cause.	From first dose of rituximab IV and SC until death from any cause (up to end of induction treatment [Up to 51.1 Months])
Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response Criteria	DFS will be assessed at the end of induction treatment in patients achieving CR/CRu and is defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause.	From the date of the initial complete response (CR)/complete response unconfirmed (CRu) until date of relapse or death from any cause (up to end of induction treatment [Up to 32.7 Months])
Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria	CR/CRu: Response assessments 4 - 6 weeks after the last dose of induction treatment will be based on the Investigator's assessment, completed according to the original International Working Group (IWG) response criteria for response assessment of lymphoma (Cheson et al. 1999).	From first dose of rituximab until first occurrence of progression or relapse (up to end of induction treatment [Up to 32 Months])
Healthcare Professional Questionnaire Score	Planned Healthcare Professional Questionnaiere was not collected during the study therefore no data to report	End of treatment (Month 24 for FL participants and Month 8 for DLBCL participants)
Patient-Reported Rituximab Administration Questionnaire (RASQ) Score	The RASQ measures the overall participant satisfaction and is a 20-item questionnaire measuring the impact of the treatment administration on 5 domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. Each question's answer is chosen from 1 (minimum)-5(maximum score indicating less severity) score range. For each domain was scored using the following formula: Domain score = [(Sum of completed item (question) responses / Number of completed items) - 1] x 100 / (Maximum possible item response value - Minimum possible item response value) The final RASQ domains is calculated using the formula: RASQ domain score = (Mean of completed item responses - 1) x 25, scores ranging from 1-100 with higher scores indicative of more positive feelings toward therapy. Lower number representing lower satisfaction and higher is the higher satisfaction by the participants.	Up to 53.8 Months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2015
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: March 29, 2015
• First Posted (Estimated): April 2, 2015

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Rituximab; Prednisone; Cyclophosphamide; Fludarabine; Doxorubicin; Vincristine
• Other Study ID Numbers: ML28964