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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BR+R<br>Induction Therapy: Rituximab Combined With Bendamustine Maintenance Treatment: Rituximab | Drug: BR for 6 cycles +R for 8 cycles<br>* 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)<br>|
| Experimental: RCHOP+R<br>Induction Therapy: Rituximab Combined With Cyclophosphamide, Vincristine, Doxorubicin, Prednisone Maintenance Treatment: Rituximab | Drug: RCHOP for 6 cycles +R for 8 cycles<br>* 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)<br>|
| Experimental: R2+R2<br>Induction Therapy: Lenalidomide Combined With Rituximab Maintenance Treatment: Lenalidomide Combined With Rituximab | Drug: R2 for 6 cycles + R2 maintenance<br>* 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)<br>|

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 |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Follicular lymphoma, Rituximab, maintenance treatment