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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02961881




Registration number
NCT02961881
Ethics application status
Date submitted
6/09/2016
Date registered
11/11/2016

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2016-002034-76
Secondary ID [2] 0 0
20140286
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - blinatumomab

Experimental: blinatumomab -


Treatment: Drugs: blinatumomab
Blinatumomab used as both continuous IV infusion and subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting-Toxicities (DLTs) After SC Administration
Timepoint [1] 0 0
Day 1 to Day 7 of Week 4
Primary outcome [2] 0 0
Number of Participants With DLTs CTCAE Grade = 3 After SC Administration
Timepoint [2] 0 0
Day 1 to Day 7 of Week 4
Primary outcome [3] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) After SC Administration
Timepoint [3] 0 0
Day 1 to end of study (approximately 17 weeks)
Secondary outcome [1] 0 0
Steady State Serum Concentration (Css) of Blinatumomab After cIV Administration
Timepoint [1] 0 0
Once at any timepoint during Day 2 of Weeks 1, 2, 3, 5 and 6
Secondary outcome [2] 0 0
Systemic Clearance (CL) of Blinatumomab After cIV Administration
Timepoint [2] 0 0
Once at any timepoint during Day 2 of Weeks 1, 2, 3, 5 and 6
Secondary outcome [3] 0 0
Maximum Observed Concentration (Cmax) of Blinatumomab After SC Administration
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Time at Which Cmax (Tmax) Occurred of Blinatumomab After SC Administration
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Area Under the Concentration-time Curve (AUC) of Blinatumomab After SC Administration for a Dosing Interval t (AUCt)
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Minimum Observed Concentration (Cmin) of Blinatumomab After SC Administration
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Apparent Clearance (CL/F) of Blinatumomab After SC Administration
Timepoint [7] 0 0
Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)
Secondary outcome [8] 0 0
Volume of Distribution Based on Terminal Phase (Vz/F) of Blinatumomab After SC Administration
Timepoint [8] 0 0
Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)
Secondary outcome [9] 0 0
Terminal Half-life (t1/2,z) of Blinatumomab After SC Administration
Timepoint [9] 0 0
Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)
Secondary outcome [10] 0 0
Accumulation Ratio of Blinatumomab After SC Administration
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Bioavailability (F) of SC Blinatumomab
Timepoint [11] 0 0
Week 4 Day 5 (pre-dose and 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose)
Secondary outcome [12] 0 0
Maximum Tolerated Dose (MTD) of SC Blinatumomab
Timepoint [12] 0 0
Day 1 to Day 7 of Week 4
Secondary outcome [13] 0 0
Number of Participants With Anti-blinatumomab Antibody Formation After SC Administration
Timepoint [13] 0 0
Predose at the re-start of cIV infusion (Week 5 Day 1)
Secondary outcome [14] 0 0
Overall Response Rate (ORR) After SC Administration
Timepoint [14] 0 0
Day 1 to end of study (approximately 17 weeks)

Eligibility
Key inclusion criteria
* 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
* Responded to initial therapy for = 1 year and relapsed after 2 or more lines of therapy, including an anti-CD20 monoclonal antibody

* Measurable disease that has not been previously irradiated on positron emission tomography- computed tomography (PET-CT), or computed tomography (CT), of at least 1.5 cm within the last 21 days before the start of IP treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
* Life expectancy greater than or equal to 3 months as determined by treating physician.
* Subjects must have adequate organ and marrow at screening as defined below:
* peripheral neutrophils >500/µL prior to start of treatment
* hemoglobin =8 g/dL
* Platelets greater than or equal to 50,000 mcL
* aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) < 5 × upper limit of normal (ULN
* Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
* Creatinine clearance greater than or equal to 50 mL/min (Cockcroft-Gault)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* Prostatic intraepithelial neoplasia without evidence of prostate cancer.
* Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or uncontrolled systemic fungal bacteria, viral, or other infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* A female who is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 48 hours (Period 1) or 96 hours (Period 2), respectively, after the last dose of blinatumomab (Female subjects of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test).
* A female of childbearing potential unwilling to use highly effective method of contraception during treatment and for an additional 48 hours (Period 1) or 96 hours (Period 2), respectively, after the last dose of blinatumomab.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/09/2021
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Epworth Healthcare - East Melbourne
Recruitment hospital [3] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
France
State/province [4] 0 0
Créteil Cedex
Country [5] 0 0
France
State/province [5] 0 0
Paris Cedex 10
Country [6] 0 0
Germany
State/province [6] 0 0
Dresden
Country [7] 0 0
Germany
State/province [7] 0 0
Frankfurt am Main
Country [8] 0 0
Germany
State/province [8] 0 0
Ulm
Country [9] 0 0
Italy
State/province [9] 0 0
Bergamo
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Brescia
Country [12] 0 0
Italy
State/province [12] 0 0
Milano
Country [13] 0 0
Italy
State/province [13] 0 0
Rozzano MI
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Leicester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02961881