A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma

NCT02961881 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 201402862016-002034-76
• Study Type: interventional
• Target: 35
• Locations: 6 countries
• Sites: 17

Brief Summary

Primary Objective:

• To evaluate the safety and tolerability of subcutaneous (SC) blinatumomab dose administrations Secondary Objectives:
• To determine pharmacokinetics (PK) with continuous intravenous (cIV) and SC administrations
• To estimate the maximum tolerated dose (MTD) tested for blinatumomab administered subcutaneously
• To determine the incidence of anti-blinatumomab antibody formation following SC administration
• To evaluate efficacy response following treatment with SC blinatumomab administration Exploratory Objective:
• To determine the pharmacodynamics (PD) time profiles for B-and T-lymphocytes as well as cytokine profiles during SC administration
• To evaluate efficacy response following treatment with SC blinatumomab administration using Lugano criteria if positron emission tomography-computed tomography (PET/CT) is used for evaluation

Conditions

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting-Toxicities (DLTs) After SC Administration

  The occurrence of any of the following toxicities during the DLT evaluation period was considered a DLT, if judged by the investigator to be related to the administration of blinatumomab: * Death * Any toxicity, regardless of grade, that lead to a participant's removal from the study by the investigator and/or sponsor * Persistent Common Terminology Criteria for Adverse Events (CTCAE) grade \>/= 2 non-hematologic adverse events (AEs) that were deemed intolerable by the participant or the treating physician and that did not respond to appropriate medical management within 5 days and lead to treatment discontinuation * Recurrent grade 2 seizures * All grade 3 and 4 AEs and laboratory abnormalities, which occurred during the SC administration portion of the treatment period with exceptions noted in protocol section 6.2.1.2.3.

  Day 1 to Day 7 of Week 4

• Number of Participants With DLTs CTCAE Grade ≥ 3 After SC Administration

  All toxicities were graded using the CTCAE version 4.0: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = fatal.

  Day 1 to Day 7 of Week 4

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) After SC Administration

  An AE was defined as any untoward medical occurrence in a clinical study participant. The AE did not necessarily have a causal relationship with study treatment. The definition of AEs included worsening of a pre-existing medical condition. TEAEs included AEs starting on or after first dose of investigational product and up to the end of study date. All AEs were graded using the CTCAE version 4.0: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = fatal.

  Day 1 to end of study (approximately 17 weeks)

Secondary Outcomes (14)

• Steady State Serum Concentration (Css) of Blinatumomab After cIV Administration

  Once at any timepoint during Day 2 of Weeks 1, 2, 3, 5 and 6

• Systemic Clearance (CL) of Blinatumomab After cIV Administration

  Once at any timepoint during Day 2 of Weeks 1, 2, 3, 5 and 6

• Maximum Observed Concentration (Cmax) of Blinatumomab After SC Administration

  Week 4 Day 1 (pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose) and Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)

• Time at Which Cmax (Tmax) Occurred of Blinatumomab After SC Administration

  Week 4 Day 1 (pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose) and Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)

• Area Under the Concentration-time Curve (AUC) of Blinatumomab After SC Administration for a Dosing Interval t (AUCt)

  Week 4 Day 1 (pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose) and Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)

Study Arms (1)

blinatumomab

EXPERIMENTAL

Drug: blinatumomab

Interventions

blinatumomab DRUG

Blinatumomab used as both continuous IV infusion and subcutaneous injection

blinatumomab

Eligibility Criteria

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

You may qualify if:

• Subject or subject's legally acceptable representative has provided informed consent.
• Age greater than or equal to 18 years old at the time of informed consent
• Subjects must have a histologically determined B cell NHL subtype as defined in the bullets below.
• In addition, they must have disease that is primary refractory after initial therapy or have relapsed disease.
• Follicular Lymphoma I, II, IIIA
• Marginal zone lymphoma (extranodal, nodal or splenic). Subjects with gastric mucosa-
• associated lymphoid tissue must have progressed after Helicobacter pylori therapy and
• radiation. Subjects with splenic marginal zone lymphoma must have prior splenectomy.
• Lymphoplasmocytic lymphoma
• Mantle cell lymphoma (\[MCL\] with the exception of aggressive MCL, defined as Ki67 \> 30%,
• or blastoid histology)
• Small lymphocytic lymphoma
• Subjects without standard therapy alternatives, or contraindicated for standard therapy by investigator, or subjects unwilling to receive standard therapy. Disease status must be 1 of the following:
• Primary refractory (at least 1 prior line of therapy)
• Relapsed within 1 year of first response

You may not qualify if:

• Currently receiving treatment in another investigational device or drug study, or less than 30 days between ending treatment on another investigational device or drug study(ies) and start of IP treatment. Other investigational procedures while participating in this study are excluded.
• Known hypersensitivity to immunoglobulins or any other component of the study drug
• Subject likely to not be available to complete all protocol required study visits or procedures to the best of the subject and investigator's knowledge
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation procedures or completion.
• Subjects who have had treatments with anti-cancer agents including rituximab or obinutuzumab and/or other monoclonal antibody or radioimmunotherapy within 6 weeks before the starting IP treatment.
• Autologous stem cell transplantation within 12 weeks before the starting IP treatment or past history of allogeneic stem cell transplantation.
• Subjects who have received anti-CD 19 targeted therapies, chimeric antigen receptor T-cell or other cellular therapies for the treatment of their lymphoma .
• Subjects with suspected or known brain metastases should be excluded from this clinical study because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
• History of or current relevant central nervous system pathology such as epilepsy, recurrent seizures, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome or psychosis.
• History of malignancy other than their lymphoma with the exception of:
• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease

Sponsors & Collaborators

• Amgen: lead

Study Sites (17)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Epworth Healthcare

East Melbourne, Victoria, 3002, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Hopital Henri Mondor

Créteil Cedex, 94010, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitätsklinikum Frankfurt/Main

Frankfurt am Main, 60590, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano MI, 20089, Italy

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: November 11, 2016
• Study Start: September 18, 2017
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: February 2, 2024
• Results First Posted: February 2, 2024

Record last verified: 2023-05

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

IT (5); FR (2); US (3); DE (3); GB (1); AU (3)