Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab

Lymphoma, Non-Hodgkin Clinical Trial

— JASMINE  

Official title:

A Randomized, Double-Blind Study Evaluating the Efficacy, Safety and Immunogenicity of ABP 798 Compared With Rituximab in Subjects With CD20 Positive B-Cell Non-Hodgkin Lymphoma (NHL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02747043
• Other study ID #: 20130109
• Secondary ID: 2013-005542-11
• Status: Completed
• Phase: Phase 3
• Start date: May 25, 2016
• Est. completion date: June 28, 2019

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a randomized, double-blind, active-controlled, multiple-dose, clinical similarity study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of ABP 798 compared with rituximab in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden.

Subjects were randomized in a 1:1 ratio to receive a 375 mg/m^2 intravenous infusion of either ABP 798 or rituximab once weekly for 4 weeks followed by dosing at weeks 12 and 20.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: June 28, 2019
• Est. primary completion date: June 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males and females 18 years of age and older

• Histological confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization

• Stage 2, 3, or 4 (per Cotswold's Modification of Ann Arbor Staging System) with measurable disease (per International Working Group)

• subjects must have a baseline scan (computed tomography [CT]) of the neck (if palpable lymph node > 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization

• subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening.

• Low tumor burden based on the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria

• largest nodal or extranodal mass = 7 cm

• no more than 3 nodal sites with diameter > 3 cm

• no splenomegaly > 16cm by CT scan and no symptomatic splenomegaly

• no significant pleural or peritoneal serous effusions by CT

• lactate dehydrogenase = upper limit of normal (ULN)

• no B symptoms (night sweats, fever [temperature > 38°C], weight loss > 10% in the previous 6 months)

Exclusion Criteria:

• Diffuse large cell component and/or Grade 3b follicular NHL

• History or known presence of central nervous system metastases

• Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or squamous or basal cell carcinoma of the skin)

• Recent infection requiring a course of systemic anti-infective agents that was completed = 7 days before randomization (with the exception of uncomplicated urinary tract infection)

• Other investigational procedures that can impact the study data, results, or patient safety while participating in this study are excluded; participation in observational studies is allowed.

• Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives (whichever is longer) since ending other investigational device or drug study(s), including vaccines, or subject is receiving other investigational agent(s)

• Previous use of either commercially available or investigational chemotherapy, biological, or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other anti-CD20 treatments)

• Systemic corticosteroid use within 3 months before randomization (inhaled are allowable)

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• ABP 798
ABP 798 was supplied as a sterile, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.
• Rituximab
Rituximab was procured from commercial supplies in the US and was supplied as a sterile, clear, colorless, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100-mg/10 mL or 500-mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.

Locations

Country	Name	City	State
Australia	Research Site	Frankston	Victoria
Australia	Research Site	Gosford	New South Wales
Australia	Research Site	Perth	Western Australia
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Stara Zagora
Canada	Research Site	Windsor	Ontario
Colombia	Research Site	Bogota	Cundinamarca
Colombia	Research Site	Medellin	Antioquia
Czechia	Research Site	Ostrava - Poruba	Severomoravsky KRAJ
Czechia	Research Site	Praha 5	Praha
France	Research Site	Bordeaux Cedex	Aquitaine
France	Research Site	Boulogne sur Mer	NORD Pas-de-calais
France	Research Site	Cesson-Sevigne	Bretagne
France	Research Site	Clermont Ferrand	Auvergne
France	Research Site	La Rochelle	Poitou-charentes
France	Research Site	Poitiers Cedex	Poitou-charentes
Georgia	Research Site	Batumi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Germany	Research Site	Augsburg	Bayern
Germany	Research Site	Flensburg	Schleswig-holstein
Germany	Research Site	Freiburg	Baden-wuerttemberg
Germany	Research Site	Kassel	Hessen
Germany	Research Site	Leipzig	Sachsen
Germany	Research Site	Münster	Nordrhein-westfalen
Germany	Research Site	Würzburg	Bayern
Greece	Research Site	Athens	Attica
Greece	Research Site	Athens	Attica
Greece	Research Site	Patra	Peloponnese
India	Research Site	Bangalore	Karnataka
India	Research Site	Bikaner	Rajasthan
India	Research Site	Mangalore	Karnataka
India	Research Site	Nashik	Maharashtra
India	Research Site	Pune	Maharashtra
India	Research Site	Surat	Gujarat
India	Research Site	Vadodara	Gujarat
Israel	Research Site	Be'er Ya'akov	Rehoboth
Italy	Research Site	Aviano	Pordenone
Italy	Research Site	Bergamo	Lombardia
Italy	Research Site	Brescia
Italy	Research Site	Candiolo	Torino
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Pesaro	Pesaro E Urbino
Italy	Research Site	Ravenna
Italy	Research Site	Rimini
Italy	Research Site	San Giovanni Rotondo	Foggia
Italy	Research Site	Terni
Japan	Research Site	Chiba-city	Chiba
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Kobe-city	Hyogo
Japan	Research Site	Maebashi-city	Gunma
Japan	Research Site	Tachikawa-city	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Tsu	MIE
Japan	Research Site	Utsunomiya City	Tochigi
Korea, Republic of	Research Site	Busan	Gyeongsangnam-do
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jinju-si	Gyeongsangnam-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul	Gyeonggi-do
Korea, Republic of	Research Site	Seoul	Gyeonggi-do
Korea, Republic of	Research Site	Ulsan
Mexico	Research Site	Chihuahua
Mexico	Research Site	Mexico City	Distrito Federal
Poland	Research Site	Gdansk	Pomorskie
Poland	Research Site	Kraków	Malopolskie
Poland	Research Site	Legnica	Dolnoslaskie
Poland	Research Site	Torun	Kujawsko-pomorskie
Romania	Research Site	Bucuresti
Romania	Research Site	Targu-Mures	Mures
Romania	Research Site	Targu-Mures	Mures
Romania	Research Site	Timisoara	Timis
Spain	Research Site	Barcelona
Spain	Research Site	Caceres
Spain	Research Site	Cadiz
Spain	Research Site	Córdoba	Cordoba
Spain	Research Site	La Laguna Tenerife	Santa CRUZ DE Tenerife
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda	Madrid
Spain	Research Site	Sabadell	Barcelona
Spain	Research Site	Salamanca
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Kyiv	Kiev
Ukraine	Research Site	Kyiv	Kiev
Ukraine	Research Site	Uzhgorod	Transcarpathia
United States	Research Site	Billings	Montana
United States	Research Site	Encinitas	California
United States	Research Site	Mount Sterling	Kentucky
United States	Research Site	Roanoke	Virginia
United States	Research Site	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Colombia,  Czechia,  France,  Georgia,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Romania,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease	Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders.; CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results.; PR was a = 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.	Post treatment up to Week 28
Secondary	Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease	Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders.; CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results.; PR was a = 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.	Week 12
Secondary	Pharmacokinetic Serum Concentrations by Visit	Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations >0.	Weeks 2, 3, 4, 12 and 20
Secondary	Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8	Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts < 20 cell/µL (0.02 * 10^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count < 20 cell/µL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.	Baseline (Day 1), Study Day 8
Secondary	Total Immunoglobulin G (IgG) Results by Visit	Samples were analyzed by a central lab.	Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Secondary	Total Immunoglobulin M (IgM) Results by Visit	Samples were analyzed by a central lab.	Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Secondary	Participants With Treatment-Emergent Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard.; IP = investigational product	Day 1 (post treatment) to Week 28
Secondary	Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs)	The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome.; Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date.	Day 1 (post treatment) to Week 28
Secondary	Number of Participants Who Developed Anti-drug Antibodies	Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay).; Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.	Baseline (Day 1), Weeks 12, 20 and 28
Secondary	Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease	PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.	Day 1 up to Week 28
Secondary	Percentage of Participants Who Survived -- Overall Survival (OS)	Percentage of participants who were alive at the end of the study.	Day 1 up to Week 28

External Links

•   AmgenTrials clinical trials website