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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02910063




Registration number
NCT02910063
Ethics application status
Date submitted
30/08/2016
Date registered
21/09/2016
Date last updated
13/01/2021

Titles & IDs
Public title
Study to Evaluate Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory (R/R) Aggressive B-Cell NHL
Scientific title
A Phase 2/3 Multi-center Study to Evaluate the Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
Secondary ID [1] 0 0
2016-002044-16
Secondary ID [2] 0 0
20150292
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-Cell Non Hodgkin 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
Mental Health 0 0 0 0
Other mental health disorders

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

Experimental: Blinatumomab - Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab is continuous infusion with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/days until the end of the cycle.


Treatment: Drugs: Blinatumomab
Blinatumomab monotherapy

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

Outcomes
Primary outcome [1] 0 0
Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR) - Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
Timepoint [1] 0 0
Up to 12 weeks after first dose of blinatumomab
Primary outcome [2] 0 0
Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR) - Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
Timepoint [2] 0 0
Up to 12 weeks after first dose of study treatment
Secondary outcome [1] 0 0
Phase 2: Overall Survival (OS) - OS was defined as the time from the date of randomization until death due to any cause.
OS was calculated using Kaplan-Meier estimates.
Timepoint [1] 0 0
From randomization until the end of study, up to 30 months
Secondary outcome [2] 0 0
Phase 2: Objective Response Rate (ORR) - ORR is inclusive of all participants who achieved CMR or those who achieved partial metabolic response (PMR), as determined by central radiographic assessment of PET/CT scans using the Lugano Classification.
Timepoint [2] 0 0
Up to 12 weeks after first dose of blinatumomab
Secondary outcome [3] 0 0
Phase 2: Progression Free Survival (PFS) - PFS was defined as the time from start of treatment with blinatumomab until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. PFS was estimated using Kaplan-Meier method.
Timepoint [3] 0 0
From first dose of blinatumomab until the end of study, up to 30 months
Secondary outcome [4] 0 0
Phase 2: Duration of Response (DOR) - DOR was calculated only for participants who achieve a response (CMR or PMR). The duration was calculated from the date a response, CMR or PMR, was first achieved until the earliest date of a disease assessment indicating disease progression or death, whichever occured first. DOR was estimated using Kaplan-Meier method.
Timepoint [4] 0 0
From first dose of blinatumomab up to 12 weeks
Secondary outcome [5] 0 0
Phase 2: Percentage of Participants Who Experienced Successful Mobilization - Successful mobilization rate was defined as the percentage of participants who initiated mobilization while in remission and without any other anti-tumor therapy where the mobilization procedure had an outcome of 'Successful'. Successful mobilization was dictated by institutional standards and defined when the target cell dose was no less than 2 x 10^6 CD34+ cells/kg.
Timepoint [5] 0 0
From first dose of blinatumomab until the end of study, up to 30 months
Secondary outcome [6] 0 0
Phase 2: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT) - The percentage of responders per investigator's review (participants who achieved either CMR or PMR during the treatment) who have undergone allogeneic (allo) HSCT or autologous (auto) HSCT while in remission and without any other anti-cancer treatment.
Timepoint [6] 0 0
From baseline HSCT until the end of study, up to 30 months
Secondary outcome [7] 0 0
Phase 2: Cumulative Incidence Function Estimate of 100-day Mortality After HSCT Presented as Percentage of Participants That Died Not Due to Relapse, With Relapse and Death Due to Relapse as Competing Events - Non-relapse mortality rate at 100 days after HSCT was calculated as the percentage of participants who died not due to relapse. Only participants who achieved a response per investigator's review and underwent autoHSCT are included.
Timepoint [7] 0 0
100 days after HSCT
Secondary outcome [8] 0 0
Phase 2: Blinatumomab Steady State Concentrations (Css) - Pharmacokinetic (PK) parameters were estimated by non compartmental analysis. The Css of blinatumomab was summarized as the observed concentrations collected after at least 24 hours after the start of continuous IV infusion or start of dose step, where appropriate.
Timepoint [8] 0 0
Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)
Secondary outcome [9] 0 0
Phase 2: Blinatumomab Clearance (CL) - Serum blinatumomab CL was calculated as CL=R0/Css,DN; where R0 is the infusion rate (µg/hr) and Css,DN is the dose normalized average Css. For the CL calculation, the Css,DN was normalized to the 112 µg/day dose in which the value of dose in units of µg/hr was used for the infusion rate.
Timepoint [9] 0 0
Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)
Secondary outcome [10] 0 0
Phase 2: Half-life of Blinatumomab
Timepoint [10] 0 0
Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)
Secondary outcome [11] 0 0
Phase 2: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) - Treatment-emergent adverse events were events with an onset after the administration of the first dose of blinatumomab.
TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL).
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL.
Grade 4 Life-threatening consequences; urgent interventions indicated.
Timepoint [11] 0 0
From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days
Secondary outcome [12] 0 0
Phase 3: Objective Response Rate (ORR)
Timepoint [12] 0 0
Up to 12 weeks after first dose of study treatment
Secondary outcome [13] 0 0
Phase 3: Progression Free Survival (PFS)
Timepoint [13] 0 0
From first dose of study treatment until the end of study, up to 30 months
Secondary outcome [14] 0 0
Phase 3: Duration of Response (DOR)
Timepoint [14] 0 0
From first dose of study treatment up to 12 weeks
Secondary outcome [15] 0 0
Phase 3: Percentage of Participants Who Experienced Successful Mobilization
Timepoint [15] 0 0
From baseline until the end of study, up to 30 months
Secondary outcome [16] 0 0
Phase 3: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT)
Timepoint [16] 0 0
From baseline HSCT until the end of study, up to 30 months
Secondary outcome [17] 0 0
Phase 3: Percentage of Participants Who Died Within 100 Days After Hematopoietic Stem Cell Transplantation (HSCT) That Was Not Due to Relapse
Timepoint [17] 0 0
100 days after HSCT
Secondary outcome [18] 0 0
Phase 3: Change From Baseline in Patient Reported Clinical Outcome Assessments Quality of Life (QOLCOA) Scores
Timepoint [18] 0 0
Up to 30 days after last dose after study treatment
Secondary outcome [19] 0 0
Phase 3: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Timepoint [19] 0 0
From first dose of study treatment until 30 days after last dose
Secondary outcome [20] 0 0
Phase 3: Serum Blinatumomab Steady State Concentration (Css)
Timepoint [20] 0 0
24 hours after first dose of blinatumomab
Secondary outcome [21] 0 0
Phase 3: Blinatumomab Clearance (CL)
Timepoint [21] 0 0
Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)
Secondary outcome [22] 0 0
Phase 3: Half-life of Blinatumomab
Timepoint [22] 0 0
Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Eligibility
Key inclusion criteria
- Biopsy proven aggressive B-cell Non-Hodgkin Lymphoma (B-NHL), including diffuse large
B-cell lymphoma (DLBCL) not otherwise specified (NOS), follicular lymphoma Grade 3B,
PMBCL, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of
indolent non-Hodgkin's Lymphoma (NHL), (including follicular, marginal zone, and
lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin
Lymphoma. The following histologies are not eligible:

- Lymphoblastic lymphoma

- Burkitt lymphoma

- Mantle cell lymphoma Any histologies not specifically mentioned must be discussed
with medical monitor.

- Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of
standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20
agent. For subjects with refractory disease and who have received radiotherapy, PET
positivity should be demonstrated no less than 6 weeks after the last dose of
radiotherapy

- Biopsy proven confirmation of relapsed disease.

- Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the
S1 setting and had a response of progressive metabolic disease (PMD), no metabolic
response (NMR), partial metabolic response (PMR) as centrally assessed by PET-/ CT
scan or received at least 1 cycle of S1 chemotherapy and had evidence of PMD as
centrally assessed. A pre-salvage scan is required to be submitted to the central
reader if a subject had only 1 cycle of pre-salvage chemotherapy.

- Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in
its largest dimension or a target extranodal lesion at least 1.0 cm in its largest
dimension

- Eastern Cooperative Oncology Group performance status less than or equal to 2

- Intention to proceed to high dose chemotherapy (HDT) and autologous hematopoietic stem
cell transplant (HSCT)

- Laboratory parameters:

Hematology:

- Absolute neutrophil count (ANC) = 1.0 x 10^9/L

- Platelets = 75 x 10^9/L

Chemistry:

- Creatinine clearance = 50 mL/min

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of
normal (ULN)

- Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with
lymphoma)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- CMR following S1 chemotherapy

- Treatment within 30 days prior to randomization with another investigational device or
drug study (ies).

- Prior anti-CD19-directed therapies

- Prior HDT with autologous HSCT

- Prior allogeneic HSCT

- Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis,
aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar
disease, organic brain syndrome, or psychosis

- Evidence of CNS involvement by NHL

- Known 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 B-NHL within the past 3 years with the exception of:

- Malignancy treated with curative intent and with no known active disease present
for = 3 years before enrollment

- Adequately treated non-melanoma skin cancer or lentigo maligna

- Adequately treated cervical carcinoma in situ

- Adequately treated breast ductal carcinoma in situ

- Prostatic intraepithelial neoplasia without evidence of prostate cancer

- Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in
situ

- Known sensitivity to immunoglobulins or any of the components to be administered
during dosing.

- Subject likely to not be available to complete all protocol-required study visits or
procedures, and/or to comply with all required procedures.

- History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that would pose a risk to subject safety
or interfere with the study evaluation, procedures or completion.

- Female subjects who are pregnant or breastfeeding or planning to become pregnant or
breastfeed, or of childbearing potential unwilling to use an effective method of
contraception while receiving, and for an additional 48 hours after the last dose of
blinatumomab.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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 2/Phase 3
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,QLD,VIC,WA
Recruitment hospital [1] 0 0
Research Site - St Leonards
Recruitment hospital [2] 0 0
Research Site - Herston
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment hospital [4] 0 0
Research Site - Parkville
Recruitment hospital [5] 0 0
Research Site - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 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
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Gent
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Italy
State/province [9] 0 0
Bergamo
Country [10] 0 0
Italy
State/province [10] 0 0
Firenze
Country [11] 0 0
Italy
State/province [11] 0 0
Genova
Country [12] 0 0
Italy
State/province [12] 0 0
Palermo
Country [13] 0 0
Italy
State/province [13] 0 0
Pisa
Country [14] 0 0
Italy
State/province [14] 0 0
Roma
Country [15] 0 0
Italy
State/province [15] 0 0
Udine
Country [16] 0 0
Puerto Rico
State/province [16] 0 0
San Juan
Country [17] 0 0
Spain
State/province [17] 0 0
Andalucía
Country [18] 0 0
Spain
State/province [18] 0 0
Castilla León
Country [19] 0 0
Spain
State/province [19] 0 0
Cataluña
Country [20] 0 0
Spain
State/province [20] 0 0
Galicia
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Murcia
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Bristol
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Nottingham
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Sheffield

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the
treatment of subjects with Relapsed/Refractory (R/R) aggressive B-NHL not achieving CMR after
2 cycles of standard platinum-based chemotherapy regimens administered as S1. This study
incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size
re-estimation. In the phase 3 part of the study, blinatumomab will be compared to
Investigator's Choice chemotherapy.

In March 2019, decision made to not proceed with phase 3.
Trial website
https://clinicaltrials.gov/show/NCT02910063
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

Summary results
Other publications