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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03298412




Registration number
NCT03298412
Ethics application status
Date submitted
12/09/2017
Date registered
2/10/2017

Titles & IDs
Public title
Effect of Blinatumomab on Minimal Residual Disease (MRD) in Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Post Autologous Hematopoietic Stem Cell Transplantation (aHSCT)
Scientific title
A Phase 2 Open-Label Study to Determine the Effect of Blinatumomab on Minimal Residual Disease in Subjects With High-risk Diffuse Large B-cell Lymphoma Post-autologous Hematopoietic Stem-cell Transplantation.
Secondary ID [1] 0 0
2016-003255-30
Secondary ID [2] 0 0
20150291
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High-risk Diffuse Large B-cell 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
Cancer 0 0 0 0
Other cancer types

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

Experimental: Blinatumomab - After a run-in period of up to 24 months to evaluate MRD status and assess eligibility for treatment assignment, participants received blinatumomab intravenous (IV) infusion at an initial dose of 9 µg/day for the first 7 days of treatment, escalated (dose-step) to 28 µg/day starting on Day 8 (Week 2), followed by a dose-step to 112 µg/day starting on Day 15 (Week 3) and continuing until completion of therapy (Day 57 of Cycle 1).

Cycle 1 of blinatumomab treatment is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval.


Treatment: Drugs: Blinatumomab
Blinatumomab is administered as a continuous IV infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MRD-Negative Rate at the End of Cycle 1
Timepoint [1] 0 0
12 weeks (84 days)
Secondary outcome [1] 0 0
Kaplan-Meier Estimate: Progression-Free Survival (PFS)
Timepoint [1] 0 0
up to 1 year from first dose of blinatumomab
Secondary outcome [2] 0 0
Kaplan-Meier Estimate: Duration of MRD-Negative Status
Timepoint [2] 0 0
up to 1 year from first dose of blinatumomab
Secondary outcome [3] 0 0
Kaplan-Meier Estimate: Overall Survival (OS)
Timepoint [3] 0 0
up to 1 year from first dose of blinatumomab
Secondary outcome [4] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
From first dose of study drug through 30 days after the last dose of study drug. The treatment duration for the participant who received blinatumomab was 57 days.

Eligibility
Key inclusion criteria
Inclusion and
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria - Part 1

Inclusion Criteria - Part 1

* Subject has provided informed consent prior to initiation of any study-specific activities/procedures or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
* Age = 18 at time of informed consent
* Biopsy-proven DLBCL excluding DLBCL that represents transformation of indolent non-Hodgkin's lymphoma (NHL) Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible
* Subject has = 1 characteristic feature of high-risk DLBCL:

* High-risk first complete remission (defined as interim positron emission tomography - computed tomography (PET-CT) positive or < complete remission to frontline chemotherapy AND achieved complete remission to platinum-containing salvage)
* Relapse within 1 year of diagnosis
* Secondary age-adjusted international prognostic index > 1
* Partial response/partial metabolic response after minimum of 2 cycles of platinum-containing salvage chemotherapy
* C-myc rearrangement
* aHSCT with high-dose chemotherapy following first (or later) salvage treatment.
* PET-CT negative (Deauville score = 3) 90 days (± 30 days) post aHSCT
* Available relapsed and/or diagnostic pathology formalin-fixed paraffin-embedded (FFPE) tumor block or slide samples at the time of enrollment including the successful identification of malignant clone sequences by the central laboratory.
* MRD plasma sample collected = 3 weeks after the post aHSCT PET-CT scan
* Eastern Cooperative Oncology Group (ECOG) performance status = 2.
* Adequate organ function determined = 3 weeks prior to enrollment defined as follows:

* Hematological:

Absolute neutrophil count (ANC) = 1.0 x 109/L Platelet count = 75 x 109/L Hemoglobin = 8 g/dL

* Renal:

Creatinine clearance = 50 mL/min Cockcroft-Gault equation

* Hepatic:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

* Subject will be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge including but not limited to:
* Completion of up to a 24-month run-in period
* Completion of all regularly scheduled study visits including blood draws for MRD assessment, clinical disease state assessment, PET-CT scans (ie, at time of MRD positivity or relapse), assignment to treatment with blinatumomab

* Other Inclusion criteria may apply. See "Inclusion and Exclusion criteria - Part 2".

Exclusion Criteria - Part 1

* Clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia,stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
* Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab
* Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
* Prior anti-CD19 directed therapies
* Prior alloHSCT
* Received radiation = 2 weeks prior to enrollment
* 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 DLBCL within the past 3 years with the following exceptions:

* 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
* Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
* 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.
* Women who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab. (Females of child bearing potential should only be included after a negative highly sensitive urine or serum pregnancy test.)
* Women of childbearing potential unwilling to use an acceptable method of effective contraception while receiving blinatumomab and for an additional 48 hours after last dose of blinatumomab. Note: The pregnancy, breastfeeding and contraceptive requirements are specific to blinatumomab. The investigator is responsible for providing the subject (male and female) with pregnancy and breastfeeding (female only) avoidance requirements for other medications given during the study.
* Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.

* Other Exclusion criteria may apply. See "Inclusion and Exclusion criteria - Part 2".

Inclusion and Exclusion Criteria - Part 2

Inclusion Criteria - Part 2

* MRD-positive assessment (by NGS analysis) at enrollment or at any time during the run-in 1 period
* PET-CT negative (defined by Deauville criteria = 3) at run-in 2 performed = 3 weeks from MRD test result available to the site at run-in 1. Historical PET-CT are allowed if performed = 6 weeks from day 1 (first dose of blinatumomab) and subject has no clinical signs or symptoms suggestive of disease progression (eg, increase in lactate dehydrogenase [LDH] not otherwise explained)
* Adequate organ function determined = 7 days prior to treatment assignment with blinatumomab as follows:

* Hematological:

ANC = 1.0 x 109/L Hemoglobin = 8 g/L Platelet count = 75 x 109/L

* Renal:

Creatinine clearance = 50 mL/min Cockcroft-Gault equation

* Hepatic:

AST and ALT < 3 x ULN Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

Exclusion Criteria - Part 2

* Subject has active infection requiring systemic therapy
* Any change in the part 1 eligibility criteria during the run-in period.

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2019
Sample size
Target
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - St Leonards
Recruitment hospital [2] 0 0
Research Site - Westmead
Recruitment hospital [3] 0 0
Research Site - Clayton
Recruitment hospital [4] 0 0
Research Site - Geelong
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
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
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Charleroi
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Belgium
State/province [7] 0 0
Liege
Country [8] 0 0
France
State/province [8] 0 0
Créteil Cedex
Country [9] 0 0
France
State/province [9] 0 0
Lille
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
France
State/province [11] 0 0
Montpellier cedex 5
Country [12] 0 0
France
State/province [12] 0 0
Paris Cedex 10
Country [13] 0 0
France
State/province [13] 0 0
Pessac Cedex
Country [14] 0 0
France
State/province [14] 0 0
Pierre Benite Cedex
Country [15] 0 0
France
State/province [15] 0 0
Rouen
Country [16] 0 0
Greece
State/province [16] 0 0
Athens
Country [17] 0 0
Greece
State/province [17] 0 0
Thessaloniki
Country [18] 0 0
Italy
State/province [18] 0 0
Bergamo
Country [19] 0 0
Italy
State/province [19] 0 0
Brescia
Country [20] 0 0
Italy
State/province [20] 0 0
Firenze
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Palermo
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
Switzerland
State/province [24] 0 0
Bellinzona
Country [25] 0 0
Switzerland
State/province [25] 0 0
Bern
Country [26] 0 0
Switzerland
State/province [26] 0 0
Lausanne
Country [27] 0 0
Switzerland
State/province [27] 0 0
Zurich

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/NCT03298412