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

NCT02910063 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 201502922016-002044-16
• Study Type: interventional
• Target: 41
• Locations: 8 countries
• Sites: 31

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.

Conditions

B-Cell Non Hodgkin Lymphoma

Keywords

Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma; Blinatumomab; Leukemia; Standard of Care; SOC; Cancer; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR)

  Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.

  Up to 12 weeks after first dose of blinatumomab

• Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR)

  Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.

  Up to 12 weeks after first dose of study treatment

Secondary Outcomes (22)

• Phase 2: Overall Survival (OS)

  From randomization until the end of study, up to 30 months

• Phase 2: Objective Response Rate (ORR)

  Up to 12 weeks after first dose of blinatumomab

• Phase 2: Progression Free Survival (PFS)

  From first dose of blinatumomab until the end of study, up to 30 months

• Phase 2: Duration of Response (DOR)

  From first dose of blinatumomab up to 12 weeks

• Phase 2: Percentage of Participants Who Experienced Successful Mobilization

  From first dose of blinatumomab until the end of study, up to 30 months

Study Arms (1)

Blinatumomab

EXPERIMENTAL

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

Interventions

Blinatumomab DRUG

Blinatumomab monotherapy

Also known as: AMG 103, Blincyto

Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (31)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Baltimore, Maryland, 21201, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Greenville, South Carolina, 29607, United States

Location

Research Site

St Leonards, New South Wales, 2065, Australia

Location

Research Site

Herston, Queensland, 4029, Australia

Location

Research Site

Melbourne, Victoria, 3004, Australia

Location

Research Site

Parkville, Victoria, 3052, Australia

Location

Research Site

Murdoch, Western Australia, 6150, Australia

Location

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Brussels, 1200, Belgium

Location

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Ghent, 9000, Belgium

Location

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Leuven, 3000, Belgium

Location

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Montreal, Quebec, H1T 2M4, Canada

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Bergamo, 24127, Italy

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Florence, 50134, Italy

Location

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Genova, 16132, Italy

Location

Research Site

Palermo, 90146, Italy

Location

Research Site

Pisa, 56100, Italy

Location

Research Site

Roma, 00161, Italy

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Udine, 33100, Italy

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San Juan, 00918, Puerto Rico

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Córdoba, Andalusia, 14004, Spain

Location

Research Site

Valladolid, Castille and León, 47012, Spain

Location

Research Site

Barcelona, Catalonia, 08025, Spain

Location

Research Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Murcia, 30008, Spain

Location

Research Site

Bristol, BS2 8ED, United Kingdom

Location

Research Site

Nottingham, NG5 1PB, United Kingdom

Location

Research Site

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Coyle L, Morley NJ, Rambaldi A, Mason KD, Verhoef G, Furness CL, Zhang A, Jung AS, Cohan D, Franklin JL. Open-Label, phase 2 study of blinatumomab as second salvage therapy in adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Leuk Lymphoma. 2020 Sep;61(9):2103-2112. doi: 10.1080/10428194.2020.1759055. Epub 2020 Jun 16.

  PMID: 32546071 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lymphoma, B-Cell; Recurrence; Leukemia; Neoplasms

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases

Limitations and Caveats

Phase 3 part of the study was not initiated after Phase 2 data was reviewed. No participants were screened or enrolled for Phase 3.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 21, 2016
• Study Start: January 23, 2017
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: January 13, 2021
• Results First Posted: January 13, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

GB (3); AU (5); US (4); PR (1); ES (7); CA (1); IT (7); BE (3)