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

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ClinicalTrials.gov Identifier: NCT02910063
Recruitment Status : Recruiting
First Posted : September 21, 2016
Last Update Posted : December 19, 2018
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.

Condition or disease Intervention/treatment Phase
B-Cell Non Hodgkin Lymphoma Drug: Blinatumomab Drug: Investigator's Choice Chemotherapy 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 332 participants
Allocation: Randomized
Intervention Model: Parallel 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
Estimated Primary Completion Date : September 3, 2021
Estimated Study Completion Date : November 30, 2021

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

Active Comparator: Investigator's Choice
Standard of care (SOC) chemotherapy per investigator's decision in the second salvage setting. Examples include but not limited to R-ICE, R-DHAP, R-GDP, R-ESHAP, R-EPOCH.
Drug: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy
Other Name: Standard of care (SOC) chemotherapy per investigator's decision in the second salvage setting. Examples include but are not limited to R-ICE, R-DHAP, R-GDP, R-ESHAP, R-EPOCH.




Primary Outcome Measures :
  1. Phase 2 and 3- Complete Metabolic Response [ Time Frame: Approximately 70 days after initiating blinatumomab. ]
    Complete metabolic response (CMR) as determined by central radiographic assessment of positron emission tomography-computed tomography (PET-CT) scans using the Lugano Classification

  2. Phase 3- Complete Metabolic Response [ Time Frame: Approximately 84 days after initiating IC chemotherapy ]
    Complete metabolic response (CMR) as determined by central radiographic assessment of positron emission tomography-computed tomography (PET-CT) scans using the Lugano Classification


Secondary Outcome Measures :
  1. Phase 3 - Overall Survival [ Time Frame: Approximately 26 months ]
    Overall Survival (OS): calculated as the time from the date of randomization until death due to any cause. Subjects who are alive at the date that triggers the analysis will be censored at the date last known to be alive. If the date last known to be alive is after the date that triggers the analysis, the subject will be censored at the analysis trigger date.

  2. Phase 2 Objective Response Rate [ Time Frame: Approximately 30 months ]
    Objective Response Rate ORR; Complete Metabolic Response Rate + Partial Metabolic Response Rate

  3. Phase 2 Progression-Free Survival [ Time Frame: Approximately 30 months ]
    Progression-free survival (PFS): calculated as the time from start of blinatumomab until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. Subjects who are alive and did not have progression will be censored at the last date of tumor assessment.

  4. Phase 2 Duration of Response [ Time Frame: Approximately 30 months ]
    Duration of response (DOR): calculated only for subjects who achieve an objective response rate (ORR.) The duration will be calculated from the date a response, complete metabolic response (CMR) or partial metabolic response (PMR), is first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurs first. Subjects who do not 2 Years have a relapse event will be censored on their last disease assessment date. If the last disease assessment date is after the date that triggers the analysis, the subject will be censored at the analysis trigger date. A sensitivity analysis will censor subjects who receive a hematopoietic stem cell transplant (HSCT) at the time of HSCT unless there is no assessment after the HSCT, in which case the last assessment prior to the HSCT will be used as the censoring time.

  5. Phase 2 Successful Mobilization Rate [ Time Frame: Approximately 30 months ]
    Successful Mobilization Rate (defined as CD34+ cell 2x10^6/kg)

  6. Phase 2 Hematopoietic Stem Cell Transplant rates (both autologous and allogeneic) [ Time Frame: Approximately 30 months ]
    Hematopoietic Stem Cell Transplant rates among subjects with post-blinatumomab complete metabolic response and partial metabolic response.

  7. Phase 2 100 Day non-relapse mortality after autologous HSCT [ Time Frame: 100 days after autologous HSCT ]
    100 Day non-relapse mortality after autologous Hematopoietic Stem Cell Transplant

  8. Phase 2 Blinatumomab concentration steady state [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab concentration steady state

  9. Phase 2 Incidence and severity of adverse events [ Time Frame: Approximately 2 Years after treatment ]
    Incidence and severity of treatment-emergent adverse events

  10. Phase 3 Objective response rate [ Time Frame: Approximately 33 months ]
    Complete or partial metabolic response

  11. Phase 3 Progression-Free Survival [ Time Frame: Approximately 33 months ]
    Progression-Free Survival calculated as the time from the date of randomization until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. Subjects who are alive and did not have progression will be censored at the last date of tumor assessment.

  12. Phase 3 Duration of Response [ Time Frame: Approximately 33 months ]
    Duration of Response is calculated only for subjects who achieve an Overall Response Rate. The duration will be calculated from the date a response, CMR or PMR, is first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurs first.

  13. Phase 3 Successful Mobilization Rate [ Time Frame: Approximately 33 months ]
    Successful mobilization rate, defined as CD34+ cell 2x10^6/kg, following protocol assigned therapy

  14. Phase 3 Hematopoietic Stem Cell Transplant rates (both autologous and allogeneic) [ Time Frame: Approximately 33 months ]
    Hematopoietic Stem Cell Transplant (HSCT) (both autologous and allogeneic) rates among responding subjects (CMR or PMR)

  15. Phase 3 Patient-reported clinical outcome assessments [ Time Frame: Approximately 4-7 months ]
    Patient-reported clinical outcome assessments quality of life (QOLCOA) using the EQ-5D tool

  16. Phase 3 Blinatumomab concentration steady state [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab concentration steady state

  17. Phase 3 Overall incidence and severity of treatment-emergent adverse events [ Time Frame: Approximately 2 years after treatment ]
    Overall incidence and severity of treatment emergent adverse events

  18. Phase 2 Blinatumomab clearance [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab clearance

  19. Phase 2 Blinatumomab half life [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab half life

  20. Phase 3 Blinatumomab clearance [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab clearance

  21. Phase 3 Blinatumomab half life [ Time Frame: Approximately 70 days post initiation of blinatumomab ]
    Blinatumomab half life


Other Outcome Measures:
  1. Phase 2 and 3 Pharmacodynamics, including descriptive analysis of quantitative and qualitative features of lymphocyte populations. [ Time Frame: Approximately 30 months ]
    Pharmacodynamics including descriptive analysis of quantitative and qualitative features of lymphocyte populations and serum or plasma concentrations of cytokines.

  2. Phase 2 and 3 Response rates and duration according to COO designation [ Time Frame: Approximately 30 months ]
    Response rates and duration according to COO designation and c-myc and bcl-2 rearrangement and overexpression, R-IPI, Secondary IPI, NCCN IPI, response to frontline therapy, duration of first remission

  3. Phase 2 and 3 • Quantitative analysis of CF CT-DNA as determined by analysis of tumor-associated mutations in CF CT-DNA from from plasma collected at various timepoints before, during, and after treatment [ Time Frame: Approximately 30 months ]
    Phase 2 and 3 • Quantitative analysis of CF CT-DNA as determined by analysis of tumor-associated mutations in CF CT-DNA from from plasma collected at various timepoints before, during, and after treatment

  4. Phase 2 and 3 c-myc and bcl-2 rearrangement as determined from pretreatment specimens [ Time Frame: Approximately 30 months ]
    Response rates and duration according to COO designation and c-myc and bcl-2 rearrangement and over expression, R-IPI, Secondary IPI, NCCN IPI, as determined from pretreatment specimens



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.For subjects enrolled in the phase 3 portion of study, pathologic samples will be submitted for central confirmation of disease histology.
  • 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


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02910063     History of Changes
Other Study ID Numbers: 20150292
2016-002044-16 ( EudraCT Number )
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
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
Aggression
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Behavioral Symptoms
Blinatumomab
Antibodies, Bispecific
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs