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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02961881
Ethics application status
Date submitted
6/09/2016
Date registered
11/11/2016
Date last updated
19/12/2019

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
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
Drug used as a treatment for relapsed/refractory B-cell precursor ALL

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

Outcomes
Primary outcome [1] 0 0
Subject grade of dose limiting toxicities (DLTs) - Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of blinatumomab.
Timepoint [1] 0 0
37 months
Primary outcome [2] 0 0
Incidence of dose limiting toxicities (DLTs)
Timepoint [2] 0 0
37 months
Primary outcome [3] 0 0
Severity of dose limiting toxicities (DLTs) - Severity of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of blinatumomab.
Timepoint [3] 0 0
37 months
Primary outcome [4] 0 0
Adverse Events
Timepoint [4] 0 0
37 months
Secondary outcome [1] 0 0
Blinatumomab PK parameters (clearance of blinatumomab) under cIV
Timepoint [1] 0 0
37 months
Secondary outcome [2] 0 0
Blinatumomab PK parameters (volume of distribution of blinatumomab) under cIV
Timepoint [2] 0 0
37 months
Secondary outcome [3] 0 0
Blinatumomab PK parameters (clearance of blinatumomab) under SC administrations
Timepoint [3] 0 0
37 months
Secondary outcome [4] 0 0
Blinatumomab PK parameters (volume of distribution of blinatumomab) under SC administrations
Timepoint [4] 0 0
37 months
Secondary outcome [5] 0 0
Maximum Tolerated Dose
Timepoint [5] 0 0
37 months
Secondary outcome [6] 0 0
Incidence of anti-blinatumomab antibodies
Timepoint [6] 0 0
37 months
Secondary outcome [7] 0 0
Overall Response Rate (ORR)
Timepoint [7] 0 0
37 months
Secondary outcome [8] 0 0
Complete Response (CR)
Timepoint [8] 0 0
37 months
Secondary outcome [9] 0 0
Partial Response (PR) as determined by best overall response (ORR) using Cheson criteria
Timepoint [9] 0 0
37 months

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

- 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

- At least 1 prior line of therapy if primary refractory or relapsed within 1 year.
Subjects who respond to initial therapy for greater than or equal to 1 year must have
had at least 2 prior 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
(Appendix D).

- 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:

- Platelets greater than or equal to 50,000 mcL

- 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
Gender
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
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
Single group
Other design features
Phase
Phase 1
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 - Concord
Recruitment hospital [2] 0 0
Research Site - East Melbourne
Recruitment hospital [3] 0 0
Research Site - 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
New Jersey
Country [3] 0 0
France
State/province [3] 0 0
Créteil Cedex
Country [4] 0 0
France
State/province [4] 0 0
Paris Cedex 10
Country [5] 0 0
Germany
State/province [5] 0 0
Dresden
Country [6] 0 0
Germany
State/province [6] 0 0
Frankfurt am Main
Country [7] 0 0
Germany
State/province [7] 0 0
Ulm
Country [8] 0 0
Italy
State/province [8] 0 0
Bergamo
Country [9] 0 0
Italy
State/province [9] 0 0
Bologna
Country [10] 0 0
Italy
State/province [10] 0 0
Brescia
Country [11] 0 0
Italy
State/province [11] 0 0
Milano
Country [12] 0 0
Italy
State/province [12] 0 0
Rozzano MI

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

• To evaluate the safety and tolerability of subcutaneous (SC) blinatumomab dose
administrations

Secondary Objectives:

- To determine pharmacokinetics (PK) with continuous intravenous (cIV) and SC
administrations

- To estimate the maximum tolerated dose (MTD) tested for blinatumomab administered
subcutaneously

- To determine the incidence of anti-blinatumomab antibody formation following SC
administration

- To evaluate efficacy response following treatment with SC blinatumomab administration

Exploratory Objective:

- To determine the pharmacodynamics (PD) time profiles for B-and T-lymphocytes as well as
cytokine profiles during SC administration

- To evaluate efficacy response following treatment with SC blinatumomab administration
using Lugano criteria if positron emission tomography-computed tomography (PET/CT) is
used for evaluation
Trial website
https://clinicaltrials.gov/show/NCT02961881
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02961881