Rituximab Maintenance Treatment of Newly Diagnosed Follicular Lymphoma After BR or RCHOP or R2: a Multicenter Clinical Study

Rituximab Maintenance Treatment of Newly Diagnosed Follicular Lymphoma After Induction Therapy of Rituximab Combined With Bendamustine (BR) or Cyclophosphamide, Vincristine, Doxorubicin, Prednisone (RCHOP) or Lenalidomide (R2): a Multicenter Clinical Study

This multi-center clinical study will evaluate the efficacy of Rituximab maintenance treatment of newly diagnosed follicular lymphoma after induction therapy of BR, RCHOP or R2.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Drug: BR for 6 cycles +R for 8 cycles; Drug: RCHOP for 6 cycles +R for 8 cycles; Drug: R2 for 6 cycles + R2 maintenance

Detailed Description

Follicular lymphoma (FL) is a lymphoma of B cells in follicular center. It is a common pathological subtype of lymphoma, and its incidence rate is only next to diffuse large B cell lymphoma (DLBCL). The initial remission rate is high, but the tumor generally recurrent, making it difficult to be completely cured. This study attempts to explore the efficacy and safety of rituximab monotherapy maintenance after BR, RCHOP, R2 regimen induction therapy in the treatment of follicular patients, and to find the best way to maximize survival benefit and reduce treatment toxicity for FL patients. The study can improve the quality of life, prolong the survival and avoid the transformation to invasive lymphoma in patients with follicular lymphoma.

• Study Type: Interventional
• Enrollment (Anticipated): 789
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: weili Zhao, PhD, MD; Phone Number: +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu, PhD, MD; Phone Number: +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed CD20 positive follicular lymphoma grade 1, 2, or 3A based on 2016 WHO classification
• Treatment naive
• Age ≥ 18 years
• Indications for treatment confirmed
• Must has measurable lesion in CT or PET-CT prior to treatment
• Considered suitable for RCHOP, BR or R2 regimens
• Informed consented

Exclusion Criteria:

• Transformed follicular lymphoma or 3B follicular lymphoma;
• HBsAg positive and / or HBcAb positive with HBV DNA titer; HCV antibody positive with HCV-RNA; or HIV positive
• Central nervous system or meninges involved
• Any drug contraindication in the treatment plan
• Patients judged by other researchers to be unsuitable for inclusion in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BR+R; Induction Therapy: Rituximab Combined With Bendamustine Maintenance Treatment: Rituximab	Drug: BR for 6 cycles +R for 8 cycles; The patients will be given Bendamustine (90mg/m2 d1,2, every 28 days for total 6 courses) combined with Rituximab (375mg/m2 d0, every 28 days for total 6 courses) followed by Rituximab (375mg/m2 d1, every 3 months for total 8 courses)
Experimental: RCHOP+R; Induction Therapy: Rituximab Combined With Cyclophosphamide, Vincristine, Doxorubicin, Prednisone Maintenance Treatment: Rituximab	Drug: RCHOP for 6 cycles +R for 8 cycles; The patients will be given RCHOP (Rituximab 375mg/m2 ivgtt, D0, Cyclophosphamide 750mg/m2, ivgtt D1, doxorubicin 50mg/m2,ivgtt D1, Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses) followed by Rituximab (375mg/m2 d1, every 3 months for total 8 courses)
Experimental: R2+R2; Induction Therapy: Lenalidomide Combined With Rituximab Maintenance Treatment: Lenalidomide Combined With Rituximab	Drug: R2 for 6 cycles + R2 maintenance; The patients will be given Lenalidomide (25mg/d, po, D1-10, every 21 days for total 6 courses) combined with Rituximab (375mg/m2 d0, every 21 days for total 6 courses) followed by Lenalidomide (25mg/d, po, D1-10, every 28 days for total 6 courses) combined with Rituximab (375mg/m2 d1, every 3 months for total 8 courses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD negative rate of bone marrow at 24 weeks	Percentage of participants with negative MRD estimated by q-RT-PCR of bone marrow	At 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events	Up to 30 days after completion of study treatment
Overall survival	Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
Overall response rate	Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria	21 days after 6 cycles of induction therapy (each cycle is 21 days)
Progression of disease within 24 months	Progression of disease within 24 months was defined as the rate of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	Baseline up to data cut-off (24 months)
Event-free survival	Event-free survival was defined as the time from the date of diagnosis until the date of the first documented day of events.	Baseline up to data cut-off (up to approximately 4 years)
Time to Progression	Time to Progression was defined as the time from the date of diagnosis until the date of the first documented day of disease progression, using 2014 Lugano criteria, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
Duration of response	Duration of response was defined as the time from the date of diagnosis until the date of the first documented day of disease relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
Time to Next Anti-lymphoma Treatment	Time to Next Anti-lymphoma Treatment was defined as the time from the date of first treatment until the date patients need to receive next anti-lymphoma treatment on the basis of investigator assessments according to 2014 Lugano criteria	Baseline up to data cut-off (up to approximately 4 years)
Progression Free Survival	Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
MRD negative rate of peripheral blood at 24 weeks	Percentage of participants with negative MRD estimated by q-RT-PCR of peripheral blood	At 24 weeks

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: April 4, 2021
• First Submitted That Met QC Criteria: April 10, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 10, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Rituximab; Follicular lymphoma; maintenance treatment
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: FL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No