Clinical Trials /

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

NCT02747043

Description:

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02747043

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab
  • 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 IDs

  • ORG STUDY ID: 20130109
  • SECONDARY ID: 2013-005542-11
  • NCT ID: NCT02747043

Conditions

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
ABP 798biosimilar to rituximabABP 798
RituximabRituxanRituximab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ABP 798ExperimentalABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
  • ABP 798
RituximabActive ComparatorRituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
  • Rituximab

Eligibility Criteria

        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)
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease
Time Frame:Post treatment up to Week 28
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease
Time Frame:Week 12
Safety Issue:
Description: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.
Measure:Pharmacokinetic Serum Concentrations by Visit
Time Frame:Weeks 2, 3, 4, 12 and 20
Safety Issue:
Description: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.
Measure:Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8
Time Frame:Baseline (Day 1), Study Day 8
Safety Issue:
Description: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.
Measure:Total Immunoglobulin G (IgG) Results by Visit
Time Frame:Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Safety Issue:
Description:Samples were analyzed by a central lab.
Measure:Total Immunoglobulin M (IgM) Results by Visit
Time Frame:Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28
Safety Issue:
Description:Samples were analyzed by a central lab.
Measure:Participants With Treatment-Emergent Adverse Events
Time Frame:Day 1 (post treatment) to Week 28
Safety Issue:
Description: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
Measure:Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs)
Time Frame:Day 1 (post treatment) to Week 28
Safety Issue:
Description: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.
Measure:Number of Participants Who Developed Anti-drug Antibodies
Time Frame:Baseline (Day 1), Weeks 12, 20 and 28
Safety Issue:
Description: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.
Measure:Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease
Time Frame:Day 1 up to Week 28
Safety Issue:
Description:PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.
Measure:Percentage of Participants Who Survived -- Overall Survival (OS)
Time Frame:Day 1 up to Week 28
Safety Issue:
Description:Percentage of participants who were alive at the end of the study.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Amgen

Trial Keywords

  • CD20 Positive B-cell Non-Hodgkin Lymphoma
  • ABP 798

Last Updated

August 18, 2020