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Trial record 1 of 1 for:    NCT02910063
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Study to Evaluate Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory (R/R) Aggressive B-Cell NHL

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: NCT02910063
Recruitment Status : Completed
First Posted : September 21, 2016
Results First Posted : January 13, 2021
Last Update Posted : January 13, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with Relapsed/Refractory (R/R) aggressive B-NHL not achieving CMR after 2 cycles of standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to Investigator's Choice chemotherapy.

In March 2019, decision made to not proceed with phase 3.


Condition or disease Intervention/treatment Phase
B-Cell Non Hodgkin Lymphoma Drug: Blinatumomab Phase 2 Phase 3

Detailed Description:

This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with R/R aggressive B-NHL not achieving CMR after standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to IC chemotherapy.The phase 2 component of the study will consist of up to a 28-day screening period, approximately 70 to 112 days of study treatment, a 30-day (+/- 3days) safety follow up, and long-term follow up that will conclude with the final analysis of the phase 3 component, estimated at 30 months after initiation of the phase 3 component. For the phase 3 component, the study will consist of up to a 28-day screening period, a treatment period of up to approximately 168 days, a 30-day safety follow-up visit, and long-term follow up. Long-term follow up will conclude with the final analysis.In the phase 2 component, enrolled subjects will receive blinatumomab monotherapy. In the phase 3 component, enrolled subjects will be randomized in a 1:1 ratio to blinatumomab or IC chemotherapy.

In March 2019, decision made to not proceed with phase 3.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Multi-center Study to Evaluate the Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
Actual Study Start Date : January 23, 2017
Actual Primary Completion Date : March 12, 2020
Actual Study Completion Date : March 12, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab is continuous infusion with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/days until the end of the cycle.
Drug: Blinatumomab
Blinatumomab monotherapy
Other Names:
  • AMG 103
  • Blincyto




Primary Outcome Measures :
  1. Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR) [ Time Frame: Up to 12 weeks after first dose of blinatumomab ]
    Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.

  2. Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR) [ Time Frame: Up to 12 weeks after first dose of study treatment ]
    Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.


Secondary Outcome Measures :
  1. Phase 2: Overall Survival (OS) [ Time Frame: From randomization until the end of study, up to 30 months ]

    OS was defined as the time from the date of randomization until death due to any cause.

    OS was calculated using Kaplan-Meier estimates.


  2. Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 12 weeks after first dose of blinatumomab ]
    ORR is inclusive of all participants who achieved CMR or those who achieved partial metabolic response (PMR), as determined by central radiographic assessment of PET/CT scans using the Lugano Classification.

  3. Phase 2: Progression Free Survival (PFS) [ Time Frame: From first dose of blinatumomab until the end of study, up to 30 months ]
    PFS was defined as the time from start of treatment with blinatumomab until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. PFS was estimated using Kaplan-Meier method.

  4. Phase 2: Duration of Response (DOR) [ Time Frame: From first dose of blinatumomab up to 12 weeks ]
    DOR was calculated only for participants who achieve a response (CMR or PMR). The duration was calculated from the date a response, CMR or PMR, was first achieved until the earliest date of a disease assessment indicating disease progression or death, whichever occured first. DOR was estimated using Kaplan-Meier method.

  5. Phase 2: Percentage of Participants Who Experienced Successful Mobilization [ Time Frame: From first dose of blinatumomab until the end of study, up to 30 months ]
    Successful mobilization rate was defined as the percentage of participants who initiated mobilization while in remission and without any other anti-tumor therapy where the mobilization procedure had an outcome of 'Successful'. Successful mobilization was dictated by institutional standards and defined when the target cell dose was no less than 2 x 10^6 CD34+ cells/kg.

  6. Phase 2: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT) [ Time Frame: From baseline HSCT until the end of study, up to 30 months ]
    The percentage of responders per investigator's review (participants who achieved either CMR or PMR during the treatment) who have undergone allogeneic (allo) HSCT or autologous (auto) HSCT while in remission and without any other anti-cancer treatment.

  7. Phase 2: Cumulative Incidence Function Estimate of 100-day Mortality After HSCT Presented as Percentage of Participants That Died Not Due to Relapse, With Relapse and Death Due to Relapse as Competing Events [ Time Frame: 100 days after HSCT ]
    Non-relapse mortality rate at 100 days after HSCT was calculated as the percentage of participants who died not due to relapse. Only participants who achieved a response per investigator's review and underwent autoHSCT are included.

  8. Phase 2: Blinatumomab Steady State Concentrations (Css) [ Time Frame: Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days) ]
    Pharmacokinetic (PK) parameters were estimated by non compartmental analysis. The Css of blinatumomab was summarized as the observed concentrations collected after at least 24 hours after the start of continuous IV infusion or start of dose step, where appropriate.

  9. Phase 2: Blinatumomab Clearance (CL) [ Time Frame: Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days) ]
    Serum blinatumomab CL was calculated as CL=R0/Css,DN; where R0 is the infusion rate (μg/hr) and Css,DN is the dose normalized average Css. For the CL calculation, the Css,DN was normalized to the 112 μg/day dose in which the value of dose in units of μg/hr was used for the infusion rate.

  10. Phase 2: Half-life of Blinatumomab [ Time Frame: Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days) ]
  11. Phase 2: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [ Time Frame: From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days ]

    Treatment-emergent adverse events were events with an onset after the administration of the first dose of blinatumomab.

    TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE).

    Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL).

    Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL.

    Grade 4 Life-threatening consequences; urgent interventions indicated.


  12. Phase 3: Objective Response Rate (ORR) [ Time Frame: Up to 12 weeks after first dose of study treatment ]
  13. Phase 3: Progression Free Survival (PFS) [ Time Frame: From first dose of study treatment until the end of study, up to 30 months ]
  14. Phase 3: Duration of Response (DOR) [ Time Frame: From first dose of study treatment up to 12 weeks ]
  15. Phase 3: Percentage of Participants Who Experienced Successful Mobilization [ Time Frame: From baseline until the end of study, up to 30 months ]
  16. Phase 3: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT) [ Time Frame: From baseline HSCT until the end of study, up to 30 months ]
  17. Phase 3: Percentage of Participants Who Died Within 100 Days After Hematopoietic Stem Cell Transplantation (HSCT) That Was Not Due to Relapse [ Time Frame: 100 days after HSCT ]
  18. Phase 3: Change From Baseline in Patient Reported Clinical Outcome Assessments Quality of Life (QOLCOA) Scores [ Time Frame: Up to 30 days after last dose after study treatment ]
  19. Phase 3: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [ Time Frame: From first dose of study treatment until 30 days after last dose ]
  20. Phase 3: Serum Blinatumomab Steady State Concentration (Css) [ Time Frame: 24 hours after first dose of blinatumomab ]
  21. Phase 3: Blinatumomab Clearance (CL) [ Time Frame: Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days) ]
  22. Phase 3: Half-life of Blinatumomab [ Time Frame: Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy proven aggressive B-cell Non-Hodgkin Lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), follicular lymphoma Grade 3B, PMBCL, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent non-Hodgkin's Lymphoma (NHL), (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin Lymphoma. The following histologies are not eligible:

    • Lymphoblastic lymphoma
    • Burkitt lymphoma
    • Mantle cell lymphoma Any histologies not specifically mentioned must be discussed with medical monitor.
  • Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
  • Biopsy proven confirmation of relapsed disease.
  • Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of progressive metabolic disease (PMD), no metabolic response (NMR), partial metabolic response (PMR) as centrally assessed by PET-/ CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PMD as centrally assessed. A pre-salvage scan is required to be submitted to the central reader if a subject had only 1 cycle of pre-salvage chemotherapy.
  • Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
  • Eastern Cooperative Oncology Group performance status less than or equal to 2
  • Intention to proceed to high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplant (HSCT)
  • Laboratory parameters:

Hematology:

  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
  • Platelets ≥ 75 x 10^9/L

Chemistry:

  • Creatinine clearance ≥ 50 mL/min
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
  • Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)

Exclusion Criteria:

  • CMR following S1 chemotherapy
  • Treatment within 30 days prior to randomization with another investigational device or drug study (ies).
  • Prior anti-CD19-directed therapies
  • Prior HDT with autologous HSCT
  • Prior allogeneic HSCT
  • Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
  • Evidence of CNS involvement by NHL
  • Known infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti hepatitis C virus positive)
  • History of malignancy other than B-NHL within the past 3 years with the exception of:

    • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment
    • Adequately treated non-melanoma skin cancer or lentigo maligna
    • Adequately treated cervical carcinoma in situ
    • Adequately treated breast ductal carcinoma in situ
    • Prostatic intraepithelial neoplasia without evidence of prostate cancer
    • Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
  • Known sensitivity to immunoglobulins or any of the components to be administered during dosing.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required procedures.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
  • Female subjects who are pregnant or breastfeeding or planning to become pregnant or breastfeed, or of childbearing potential unwilling to use an effective method of contraception while receiving, and for an additional 48 hours after the last dose of blinatumomab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02910063


Locations
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United States, California
Research Site
Duarte, California, United States, 91010
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21201
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Research Site
Greenville, South Carolina, United States, 29607
Australia, New South Wales
Research Site
St Leonards, New South Wales, Australia, 2065
Australia, Queensland
Research Site
Herston, Queensland, Australia, 4029
Australia, Victoria
Research Site
Melbourne, Victoria, Australia, 3004
Research Site
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Research Site
Murdoch, Western Australia, Australia, 6150
Belgium
Research Site
Bruxelles, Belgium, 1200
Research Site
Gent, Belgium, 9000
Research Site
Leuven, Belgium, 3000
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H1T 2M4
Italy
Research Site
Bergamo, Italy, 24127
Research Site
Firenze, Italy, 50134
Research Site
Genova, Italy, 16132
Research Site
Palermo, Italy, 90146
Research Site
Pisa, Italy, 56100
Research Site
Roma, Italy, 00161
Research Site
Udine, Italy, 33100
Puerto Rico
Research Site
San Juan, Puerto Rico, 00918
Spain
Research Site
Cordoba, Andalucía, Spain, 14004
Research Site
Valladolid, Castilla León, Spain, 47012
Research Site
Barcelona, Cataluña, Spain, 08025
Research Site
Santiago de Compostela, Galicia, Spain, 15706
Research Site
Madrid, Spain, 28034
Research Site
Madrid, Spain, 28041
Research Site
Murcia, Spain, 30008
United Kingdom
Research Site
Bristol, United Kingdom, BS2 8ED
Research Site
Nottingham, United Kingdom, NG5 1PB
Research Site
Sheffield, United Kingdom, S10 2JF
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] May 7, 2019
Statistical Analysis Plan  [PDF] September 23, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02910063    
Other Study ID Numbers: 20150292
2016-002044-16 ( EudraCT Number )
First Posted: September 21, 2016    Key Record Dates
Results First Posted: January 13, 2021
Last Update Posted: January 13, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
Blinatumomab
Leukemia
Standard of Care
SOC
Cancer
Chemotherapy
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Aggression
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Behavioral Symptoms
Blinatumomab
Antineoplastic Agents