Clinical trial NCT02809053: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Follicular
Keywords: low tumor burden follicular lymphoma (LTBFL)
Lead sponsor: Archigen Biotech Limited
Sponsor class: INDUSTRY
First posted: 2016-06-22
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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)
2. 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).
3. 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:

1. Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody.
2. Prior radiotherapy completed \<28 days before study enrollment.
3. Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation.
4. Concomitant disease which requires continuous therapy with corticosteroids at doses equivalent to prednisolone \>20 mg/day.
5. Transformation to high-grade lymphoma secondary to previously untreated low-grade lymphoma.
6. 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.
7. Patients with a body surface area \>3.0 m2.
8. Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.
9. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening.
10. 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).
11. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.
12. Confirmed current active tuberculosis (TB)
13. Central nervous system (CNS) or meningeal involvement, or cord compression by the lymphoma; history of CNS lymphoma
14. 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).
15. 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.
16. Uncontrolled or severe hypertension, or cerebrovascular disease.
17. Serious underlying medical conditions that, per the Investigator's discretion, could impair the ability of the patient to participate in the trial
18. 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.
19. 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.
20. Receipt of a live/attenuated vaccine within 6 weeks prior to the screening visit.
21. Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period or within 12 months after the last infusion of study drug.
22. 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.

Primary outcomes:
measure: Overall Response Rate (ORR) at Week 28
timeFrame: Baseline (Day 0) to Week 28.
Secondary outcomes:
measure: Overall Response Rate (ORR) at Week 12
timeFrame: Baseline (Day 0) to Week 12
measure: Complete Response (CR) at Weeks 12 and 28
timeFrame: Baseline (Day 0) to Week 12 and Week 28.
measure: Partial Response (PR) at Weeks 12 and 28
timeFrame: Baseline (Day 0) to Week 12 and Week 28.
measure: Stable Disease (SD) at Weeks 12 and 28
timeFrame: Baseline (Day 0) to Week 12 and Week 28.
measure: Progressive Disease (PD) at 12 and 28 Weeks
timeFrame: Baseline (Week 0)to Week 12 and Week 28.
measure: Time to Event (TTE)
timeFrame: Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner
Other outcomes:
measure: Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4).
timeFrame: Baseline (Day 0) to dosing on Week 1 and Week 4
measure: Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4).
timeFrame: Baseline (Day 0) to dosing on Week 1 and Week 4
measure: Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).
timeFrame: Baseline (Day 0) to dosing on Week 1 and Week 4
measure: Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax).
timeFrame: Baseline (Day 0) to dosing on Week 1 and Week 4
measure: Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough).
timeFrame: Baseline (Day 0) to Days 1, 8, 15, 22 and 29
measure: Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
timeFrame: Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
measure: Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
timeFrame: Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
measure: Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
timeFrame: Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
measure: Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
timeFrame: Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
measure: Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit
timeFrame: Pre-dose on Day 1 to Weeks 5, 12, 20 and 28.
measure: Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time
timeFrame: Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
measure: Exploratory Analyses of Tumor Response and Time to Event
timeFrame: Baseline (Day 0) to Week 28
measure: Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28.
timeFrame: Baseline (Day 0) to Week 28
Locations:
city: Whittier
country: United States
facility: Research site
state: California
city: Canberra
country: Australia
facility: Research Site
state: Australian Capital Territory
city: Temuco
country: Chile
facility: Research site
state: Araucania
city: Hradec Kralove
country: Czechia
facility: Research site
city: Praha
country: Czechia
facility: Research site
city: Praha
country: Czechia
facility: Reasearch site
city: Libourne Cedex
country: France
facility: Research site
state: Gironde
city: Poitiers
country: France
facility: Research site
state: Vienne
city: Hamburg
country: Germany
facility: Research site
city: Budapest
country: Hungary
facility: Research site
city: San Giovanni Rotondo
country: Italy
facility: Research site
state: Foggia
city: Terni
country: Italy
facility: Research site
city: Busan
country: Korea, Republic of
facility: Research site
city: Seoul
country: Korea, Republic of
facility: Research site
city: Seoul
country: Korea, Republic of
facility: Research site
city: Mexico City
country: Mexico
facility: Research site
state: Distrito Federal
city: Pretoria
country: South Africa
facility: Research site
state: Gauteng
city: L'Hospitalet de Llobregat
country: Spain
facility: Research site
state: Barcelona
city: Cádiz
country: Spain
facility: Research site
city: Madrid
country: Spain
facility: Research site
city: Ankara
country: Turkey
facility: Research site
city: Istanbul
country: Turkey
facility: Research site
city: Mersin
country: Turkey
facility: Research site
city: Samsun
country: Turkey
facility: Research site
city: Norwich
country: United Kingdom
facility: Research site
state: Norfolk
Study officials:
References: