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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03298412
Ethics application status
Date submitted
12/09/2017
Date registered
26/09/2017
Date last updated
7/11/2018

Titles & IDs
Public title
Effect of Blinatumomab on MRD in DLBCL Subjects Post 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

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

Experimental: Blinatumomab - Blinatumomab is administered as a continuous intravenous (IV) infusion.


Treatment: Drugs: Blinatumomab
Blinatumomab will be supplied as 4 mL single-use sterile glass injection vials. Blinatumomab is administered as a continuous intravenous (IV) infusion.
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. The initial dose of blinatumomab will be 9 µg/day for the first 7 days of treatment. Blinatumomab dose will then be 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).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Minimal residual disease - To determine minimal residual disease (MRD) negative rate following blinatumomab treatment in high-risk Diffuse Large B-cell Lymphoma (DLBCL) subjects who are MRD-positive post-autologous hematopoietic stem cell transplantation (aHSCT).
Timepoint [1] 0 0
Cycle 1 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 (day 57 to 84).
Secondary outcome [1] 0 0
Progression-free survival - To describe the efficacy of blinatumomab in relation to progression-free survival
Timepoint [1] 0 0
Cycle 1 is 12 weeks in duration, including 8 weeks (56 days) of blinatumomab IV infusion, followed by a 4-week (28 day) treatment-free interval (day 57 to 84). Follow up visits will then occur every 3 months for a maximum of 1 year from the first dose.
Secondary outcome [2] 0 0
Duration of MRD-negative status - To describe the efficacy of blinatumomab in relation to MRD-negative status
Timepoint [2] 0 0
Run in part 1 to determine MRD status can last up to 24 months
Secondary outcome [3] 0 0
Overall Survival - To describe the efficacy of blinatumomab in relation to overall survival
Timepoint [3] 0 0
Cycle 1 is 12 weeks in duration, including 8 weeks (56 days) of blinatumomab IV infusion, followed by a 4-week (28 day) treatment-free interval (day 57 to 84). Follow up visits will then occur every 3 months for a maximum of 1 year from the first dose.
Secondary outcome [4] 0 0
Adverse Events - Incidence, grade and severity of treatment emergent adverse events
Timepoint [4] 0 0
Cycle 1 is 12 weeks in duration, including 8 weeks (56 days) of blinatumomab IV infusion, followed by a 4-week (28 day) treatment-free interval (day 57 to 84). Follow up visits will then occur every 3 months for a maximum of 1 year from the first dose.

Eligibility
Key inclusion criteria
Inclusion and
Minimum age
18 Years
Maximum age
100 Years
Gender
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 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 PET-CT positive or <
complete remission to frontline chemotherapy AND achieved complete remission to
platinum-containing salvage)

- Relapse within 1 year of diagnosis

- Secondary aaIPI > 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 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
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
Recruiting
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,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
Zuerich

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

Ethics approval
Ethics application status

Summary
Brief summary
The study will estimate the minimal residual disease (MRD)-negative response rate after
treatment with blinatumomab in subjects with high-risk DLBCL who are MRD-positive following
autologous hematopoietic stem cell transplantation (aHSCT). The clinical hypothesis is that
the MRD-negative response rate will be greater than 10%. Achieving an MRD-negative response
rate of 30% would be of scientific and clinical interest.
Trial website
https://clinicaltrials.gov/show/NCT03298412
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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable