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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03340766




Registration number
NCT03340766
Ethics application status
Date submitted
23/10/2017
Date registered
14/11/2017

Titles & IDs
Public title
Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adults With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Scientific title
A Phase 1b Open Label Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adult Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Secondary ID [1] 0 0
2016-002191-27
Secondary ID [2] 0 0
20150290
Universal Trial Number (UTN)
Trial acronym
HARBOUR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) 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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Blinatumomab
Treatment: Drugs - Pembrolizumab

Experimental: Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab - Participants received blinatumomab administered as a continuous intravenous infusion (CIVI) for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days then 28 µg/day for the remaining days of treatment.

Starting on Day 15 participants also received 200 mg pembrolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) until disease progression or for up to 35 cycles.

Experimental: Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab - Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 56 µg/day for the remaining days of treatment.

Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Experimental: Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab - Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 112 µg/day for the remaining days of treatment.

Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Experimental: Expansion Cohort - This cohort will test the maximum tolerated dose of blinatumomab in combination with pembrolizumab identified in Part 1 of the study.


Treatment: Drugs: Blinatumomab
Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Treatment: Drugs: Pembrolizumab
One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

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)
Timepoint [1] 0 0
The DLT evaluation period was 42 days from initiation of pembrolizumab treatment (day 15 for Cohort Ia and day 19 for Cohorts IIa and IIIa)
Secondary outcome [1] 0 0
Objective Response Rate During the First 12 Weeks Using Revised Response Criteria
Timepoint [1] 0 0
First 12 weeks of of blinatumomab treatment
Secondary outcome [2] 0 0
Objective Response Rate During the First 12 Weeks Using the Lugano Classification
Timepoint [2] 0 0
First 12 weeks of of blinatumomab treatment
Secondary outcome [3] 0 0
Objective Response Rate During the Treatment Period Using Revised Response Criteria
Timepoint [3] 0 0
From study day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Secondary outcome [4] 0 0
Objective Response Rate During the Treatment Period Using the Lugano Classification
Timepoint [4] 0 0
From study day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Secondary outcome [5] 0 0
Complete Response Rate During the First 12 Weeks Using the Revised Response Criteria
Timepoint [5] 0 0
First 12 weeks of of blinatumomab treatment
Secondary outcome [6] 0 0
Complete Response Rate During the First 12 Weeks Using the Lugano Classification
Timepoint [6] 0 0
First 12 weeks of of blinatumomab treatment
Secondary outcome [7] 0 0
Complete Response Rate During the Treatment Period Using the Revised Response Criteria
Timepoint [7] 0 0
From study day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Secondary outcome [8] 0 0
Complete Response Rate During the Treatment Period Using the Lugano Classification
Timepoint [8] 0 0
From study day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Secondary outcome [9] 0 0
Progression Free Survival by the Revised Response Criteria
Timepoint [9] 0 0
From first dose of blinatumomab up to the data cut-off date of 17 November 2020; maximum time on follow-up for PFS was 24.4, 16.4, and 6.7 months in each cohort, respectively.
Secondary outcome [10] 0 0
Progression Free Survival Using the Lugano Classification
Timepoint [10] 0 0
From first dose of blinatumomab up to the data cut-off date of 17 November 2020; maximum time on follow-up was 3.3 months.
Secondary outcome [11] 0 0
Overall Survival
Timepoint [11] 0 0
From first dose of blinatumomab up to the data cut-off date of 17 November 2020; maximum time on follow-up for OS was 29.7, 16.4, and 6.7 months in each cohort respectively.
Secondary outcome [12] 0 0
Duration of Response Response for Participants Who Achieved CR/PR Using the Revised Response Criteria
Timepoint [12] 0 0
Up to the data cut-off date of 17 November 2020; Maximum time on follow-up for DOR was 22.3, 14.2, and 4.3 months in each cohort, respectively.
Secondary outcome [13] 0 0
Duration of Response for Participants Who Achieved CR/PR Using the Lugano Classification
Timepoint [13] 0 0
Up to the data cut-off date of 17 November 2020; Maximum time on follow-up for DOR was 1 month.
Secondary outcome [14] 0 0
Blinatumomab Steady State Concentration
Timepoint [14] 0 0
Day 2 for 9 µg/day Css (all cohorts), days 10, 15, 22, 29, and 43 for 28 µg/day Css (Cohort Ia), day 10 for 28 µg/day Css (Cohorts IIa and IIIa), and days 19, 26, and 40 for 56 µg/day and 112 µg/day Css (Cohorts IIa and IIIa respectively).
Secondary outcome [15] 0 0
Blinatumomab Clearance
Timepoint [15] 0 0
Day 2 for 9 µg/day Css (all cohorts), days 10, 15, 22, 29, and 43 for 28 µg/day Css (Cohort Ia), day 10 for 28 µg/day Css (Cohorts IIa and IIIa), and days 19, 26, and 40 for 56 µg/day and 112 µg/day Css (Cohorts IIa and IIIa respectively).
Secondary outcome [16] 0 0
Pembrolizumab Peak Plasma Concentration
Timepoint [16] 0 0
Pembrolizumab cycle 1 day 1 (study day 15 for Cohort Ia, study day 19 for Cohorts IIa and IIIa) and cycle 8 day 1 (study day 162 for Cohort Ia and day 166 for Cohorts IIa and IIIa) within approximately 30 minutes after the end of the infusion.
Secondary outcome [17] 0 0
Pembrolizumab Minimum Plasma Concentration
Timepoint [17] 0 0
Pre-dose on pembrolizumab cycles 2, 4, 6, 8, and 12 (Study days 36, 78, 120, 162, and 246, respectively for Cohort Ia and study days 40, 82, 124, 166, and 250, respectively, for Cohorts IIa and IIIa)

Eligibility
Key inclusion criteria
* Have histologically confirmed diffuse large B-cell lymphoma that is either:
* Refractory after at least one regimen of systemic chemotherapy and/or targeted therapy, or
* In first or later relapse if have received at least 2 systemic regimens since time of diagnosis, or
* Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT) with adequate organ function after proximity to transplantation time exclusions
* Have measurable disease
* Eastern Cooperative Oncology Group (ECOG) performance status = 2
* Life expectancy of = 12 weeks in the opinion of the Investigator
* Biopsy proven DLBCL (biopsy proven at least at primary diagnosis of DLBCL)

Other Inclusion Criteria May Apply
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Richter's transformation (DLBCL arising in the setting of prior chronic lymphocytic leukemia) or primary mediastinal B cell lymphoma (PMBCL)
* History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
* Has a diagnosis of immunodeficiency or has received systemic steroid therapy (in excess of 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol specified therapy.
* Has undergone prior allogeneic HSCT:
* within the last 5 years OR
* greater than 5 years ago but has active graft versus host disease (GvHD) requiring systemic treatment.
* Has received autologous HSCT within 6 weeks prior to start of treatment.

Other Exclusion Criteria May Apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Other
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - St Leonards
Recruitment hospital [3] 0 0
Research Site - Adelaide
Recruitment hospital [4] 0 0
Research Site - East Melbourne
Recruitment hospital [5] 0 0
Research Site - Geelong
Recruitment hospital [6] 0 0
Research Site - Melbourne
Recruitment hospital [7] 0 0
Research Site - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
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
South Carolina
Country [3] 0 0
France
State/province [3] 0 0
Créteil Cedex
Country [4] 0 0
France
State/province [4] 0 0
Nantes Cedex 1
Country [5] 0 0
France
State/province [5] 0 0
Pierre-Benite
Country [6] 0 0
Germany
State/province [6] 0 0
Heidelberg
Country [7] 0 0
Germany
State/province [7] 0 0
Ulm
Country [8] 0 0
Germany
State/province [8] 0 0
Würzburg
Country [9] 0 0
Netherlands
State/province [9] 0 0
Maastricht
Country [10] 0 0
Netherlands
State/province [10] 0 0
Rotterdam
Country [11] 0 0
Spain
State/province [11] 0 0
Cantabria
Country [12] 0 0
Spain
State/province [12] 0 0
Castilla León
Country [13] 0 0
Spain
State/province [13] 0 0
Cataluña
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

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 URL 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.