Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02747043
Recruitment Status : Completed
First Posted : April 21, 2016
Results First Posted : August 18, 2020
Last Update Posted : August 18, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE April 19, 2016
First Posted Date  ICMJE April 21, 2016
Results First Submitted Date  ICMJE June 26, 2020
Results First Posted Date  ICMJE August 18, 2020
Last Update Posted Date August 18, 2020
Actual Study Start Date  ICMJE May 25, 2016
Actual Primary Completion Date June 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2020)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
Risk difference (RD) of objective response rate (ORR) [ Time Frame: Week 28 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2020)
  • Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease [ Time Frame: Week 12 ]
    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.
  • Pharmacokinetic Serum Concentrations by Visit [ Time Frame: Weeks 2, 3, 4, 12 and 20 ]
    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.
  • 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 ]
    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.
  • Total Immunoglobulin G (IgG) Results by Visit [ Time Frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 ]
    Samples were analyzed by a central lab.
  • Total Immunoglobulin M (IgM) Results by Visit [ Time Frame: Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28 ]
    Samples were analyzed by a central lab.
  • Participants With Treatment-Emergent Adverse Events [ Time Frame: Day 1 (post treatment) to Week 28 ]
    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
  • Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) [ Time Frame: Day 1 (post treatment) to Week 28 ]
    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.
  • Number of Participants Who Developed Anti-drug Antibodies [ Time Frame: Baseline (Day 1), Weeks 12, 20 and 28 ]
    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.
  • Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease [ Time Frame: Day 1 up to Week 28 ]
    PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.
  • Percentage of Participants Who Survived -- Overall Survival (OS) [ Time Frame: Day 1 up to Week 28 ]
    Percentage of participants who were alive at the end of the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
  • Risk difference of ORR [ Time Frame: Week 12 ]
  • Serum concentrations [ Time Frame: Predose and after end of infusion at week 12 ]
  • Percent of subjects with complete depletion of CD19 cell count and total Immunoglobin G (IgG) and IgM antibody levels [ Time Frame: Baseline to study day 8 ]
  • Subject incidence of treatment-emergent AEs and serious adverse events [ Time Frame: Up to Week 28 ]
  • Clinically significant changes in laboratory values and vital signs [ Time Frame: Up to Week 28 ]
  • Incidence of anti-drug antibodies [ Time Frame: Up to Week 28 ]
  • On study progression-free survival [ Time Frame: Up to Week 28 ]
  • On study overall survival [ Time Frame: Up to Week 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab
Official Title  ICMJE 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)
Brief 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Non-Hodgkin
Intervention  ICMJE
  • 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.
    Other Name: biosimilar to rituximab
  • Biological: 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.
    Other Name: Rituxan
Study Arms  ICMJE
  • Experimental: ABP 798
    ABP 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.
    Intervention: Biological: ABP 798
  • Active Comparator: Rituximab
    Rituximab 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.
    Intervention: Biological: Rituximab
Publications * Niederwieser D, Hamm C, Cobb P, Mo M, Forsyth C, Tucci A, Hanes V, Delwail V, Hajek R, Chien D. Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product. Target Oncol. 2020 Oct;15(5):599-611. doi: 10.1007/s11523-020-00748-4. Erratum in: Target Oncol. 2020 Dec;15(6):807.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2019)
256
Original Estimated Enrollment  ICMJE
 (submitted: April 19, 2016)
250
Actual Study Completion Date  ICMJE June 28, 2019
Actual Primary Completion Date June 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   Colombia,   Czechia,   France,   Georgia,   Germany,   Greece,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Poland,   Romania,   Spain,   Ukraine,   United States
Removed Location Countries Czech Republic,   New Zealand
 
Administrative Information
NCT Number  ICMJE NCT02747043
Other Study ID Numbers  ICMJE 20130109
2013-005542-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP