A Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the Efficacy, Safety, and Immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in Patients With Low Tumor Burden Follicular Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is a Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the statistical equivalence of efficacy, safety and immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in asymptomatic patients with Low Tumor Burden Follicular Lymphoma.

Detailed Description
-----------------
This is a Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the statistical equivalence of efficacy, safety and immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in asymptomatic patients with Low Tumor Burden Follicular Lymphoma. Patients will be randomized in a 1:1 ratio to receive study drug once a week for 4 weeks, and will then be followed up for up to 52 weeks after the first dose. Randomization will be stratified by inclusion in the PK/PD sub-population and Follicular lymphoma international prognostic index 2 (FLIPI-2) score. Visits are scheduled at Weeks 1, 2, 3, and 4 (study drug infusion visits), and then at Weeks 5, 12, 20, 28, 36, and 52 (i.e., End of Study [EOS]). Efficacy response assessments will be performed at Weeks 12 and 28, while safety assessments will continue until end of Study (EOS). The primary objectives is to compare the efficacy of SAIT101 with rituximab licensed in the European Union (hereafter designated MabThera®, brand name in EU) when administered as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTBFL) and the secondary objectives is to evaluate SAIT101 versus MabThera® with respect to safety and tolerability, immunogenicity and Pharmacokinetics (PK)/Pharmacodynamics (PD) in a sub-population of patients.

Official Title
-----------------
A Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the Efficacy, Safety, and Immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in Patients With Low Tumor Burden Follicular Lymphoma

Conditions
-----------------
Lymphoma, Follicular

Intervention / Treatment
-----------------
* Biological: SAIT101
* Biological: MabThera®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically-confirmed Low Tumor Burden Follicular Lymphoma, without B symptoms, Ann Arbor stage II to Non-Hodgkin's Lymphoma (NHL) (CD20+ Follicular Lymphoma of Grades 1, 2, or 3a) Low tumor burden according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria defined as: Normal serum lactate dehydrogenase (LDH) No mass ≥7 cm. Less than 3 nodal sites, each with diameter >3 cm No systemic or B symptoms (fever >38°C for 3 consecutive days; recurrent, drenching night sweats; unintentional weight loss exceeding 10% body weight in the last 6 months. No splenomegaly ≥16 cm by CT scan. No risk of vital organ compression. No pleural or peritoneal serous effusion. No leukemic phase >5,000/µL circulating tumor cells. No cytopenias (defined as platelets <100,000/mm3, hemoglobin <10 g/dL, or absolute neutrophil count <1,500/mm3). Patients not previously treated for their FL, including any previous treatment for FL under clinical trials except localized radiation therapy for previous limited stage disease. Exclusion Criteria: Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody. Prior radiotherapy completed <28 days before study enrollment. Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation. Concomitant disease which requires continuous therapy with corticosteroids at doses equivalent to prednisolone >20 mg/day. Transformation to high-grade lymphoma secondary to previously untreated low-grade lymphoma. Prior or concomitant malignancies within 5 years prior to screening, with the exceptions of non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated breast cancer in situ, and localized prostate cancer stage T1c, provided that the patient underwent curative treatment and remains relapse free. Patients with a body surface area >3.0 m2. Major surgery (excluding lymph node biopsy) within 28 days prior to randomization. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening. Acute, severe infection (e.g., sepsis and opportunistic infections), or active, chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., herpes zoster). Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology. Confirmed current active tuberculosis (TB) Central nervous system (CNS) or meningeal involvement, or cord compression by the lymphoma; history of CNS lymphoma History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the trial drug (e.g., hypersensitivity or allergy to murine products). Patients who have significant cardiac disease, including but not limited to history of congestive heart failure (New York Heart Association Class III/IV; see Appendix 7), unstable angina, or uncontrolled cardiac arrhythmia. Uncontrolled or severe hypertension, or cerebrovascular disease. Serious underlying medical conditions that, per the Investigator's discretion, could impair the ability of the patient to participate in the trial Any other co-existing medical or psychological condition(s) that will preclude participation in the study or compromise ability to give informed consent and/or comply with study procedures. Treatment with any investigational medicinal product (IMP) within 4 weeks prior to initiation of 1st infusion of study drug, or treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the 1st infusion of study drug. Receipt of a live/attenuated vaccine within 6 weeks prior to the screening visit. Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period or within 12 months after the last infusion of study drug. Patients who are investigational site staff members directly involved in the conduct of the trial, and their family members, site staff members otherwise supervised by the investigator, or patients who are Archigen employees directly involved in the conduct of the trial.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAIT101<br> | Biological: SAIT101<br>* Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22<br>|
| Active Comparator: MabThera®<br> | Biological: MabThera®<br>* Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22<br>* Other names: Rituximab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) at Week 28 | Overall Response Rate (ORR) (Complete Response [CR] + Partial Response [PR]) at Week 28, as defined by International Working Group (IWG) criteria 2007. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable. | Baseline (Day 0) to Week 28. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) at Week 12 | Overall Response Rate (ORR) = Complete Response (CR) + Partial Response (PR). Tumour assessments were assessed by central imaging review per the International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable. | Baseline (Day 0) to Week 12 | 
| Complete Response (CR) at Weeks 12 and 28 | Efficacy Endpoint: Complete Response (CR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. | Baseline (Day 0) to Week 12 and Week 28. | 
| Partial Response (PR) at Weeks 12 and 28 | Efficacy Endpoint: Partial Response (PR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. | Baseline (Day 0) to Week 12 and Week 28. | 
| Stable Disease (SD) at Weeks 12 and 28 | Efficacy endpoint: number of participants with Stable Disease (SD) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. | Baseline (Day 0) to Week 12 and Week 28. | 
| Progressive Disease (PD) at 12 and 28 Weeks | Efficacy endpoint: number of participants with Progressive Disease (PD) at 12 and 28 Weeks. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. | Baseline (Week 0)to Week 12 and Week 28. | 
| Time to Event (TTE) | Time to Event (TTE) is defined as the time of randomisation to the date when an event occurred for a maximum follow-up period of 32 weeks from baseline; an event is disease progression, death due to any cause, or the start of new treatment for follicular lymphoma, whichever comes first. | Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
low tumor burden follicular lymphoma (LTBFL)