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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04521231




Registration number
NCT04521231
Ethics application status
Date submitted
18/08/2020
Date registered
20/08/2020

Titles & IDs
Public title
A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients
Scientific title
A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
Secondary ID [1] 0 0
2019-004780-52
Secondary ID [2] 0 0
20180257
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B Cell Precursor Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
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: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1) - Cohorts of at least 3 participants each will be treated with escalating doses of bilinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.

Experimental: Dose Expansion Phase: Blinatumomab SC1 - Up to 4 cohorts of participants with R/R B-ALL will be enrolled to the preliminary recommended phase 2 dose (RP2D) and schedule determined from dose escalation phase. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.

Experimental: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations - 1 cohort of participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the RP2D determined from the dose expansion phase, in participants with R/R B-ALL.


Treatment: Drugs: Blinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 29 days
Primary outcome [2] 0 0
Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
Timepoint [2] 0 0
Up to approximately 28 weeks
Primary outcome [3] 0 0
Dose Escalation Phase: Number of participants who experience one or more serious TEAEs
Timepoint [3] 0 0
Up to approximately 28 weeks
Primary outcome [4] 0 0
Dose Escalation Phase: Number of participants who experience one or more treatment-related treatment-emergent adverse events
Timepoint [4] 0 0
Up to approximately 28 weeks
Primary outcome [5] 0 0
Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs)
Timepoint [5] 0 0
Up to approximately 28 weeks
Primary outcome [6] 0 0
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission (CR)
Timepoint [6] 0 0
Up to 68 days
Primary outcome [7] 0 0
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission with partial hematological recovery (CRh)
Timepoint [7] 0 0
Up to 68 days
Primary outcome [8] 0 0
Phase 2 Ph-IIC: Maximum concentration (Cmax) of blinatumomab SC1 and SC2
Timepoint [8] 0 0
Up to approximately 4 weeks
Primary outcome [9] 0 0
Phase 2 Ph-IIC: Average concentration (Cavg) of blinatumomab SC1 and SC2
Timepoint [9] 0 0
Up to approximately 4 weeks
Primary outcome [10] 0 0
Phase 2 Ph-IIC: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2
Timepoint [10] 0 0
Up to approximately 4 weeks
Primary outcome [11] 0 0
Phase 2 Ph-IIC: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2
Timepoint [11] 0 0
Up to approximately 4 weeks
Secondary outcome [1] 0 0
Dose Escalation Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab
Timepoint [1] 0 0
Up to approximately 28 weeks
Secondary outcome [2] 0 0
Dose Escalation Phase: Cmax of blinatumomab
Timepoint [2] 0 0
Up to approximately 28 weeks
Secondary outcome [3] 0 0
Dose Escalation Phase: Tmax of blinatumomab
Timepoint [3] 0 0
Up to approximately 28 weeks
Secondary outcome [4] 0 0
Dose Escalation Phase: AUC of blinatumomab
Timepoint [4] 0 0
Up to approximately 28 weeks
Secondary outcome [5] 0 0
Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh
Timepoint [5] 0 0
Up to 68 days
Secondary outcome [6] 0 0
Dose Escalation, Dose Expansion, and Ph-IIC: Number of participants with incidence of anti-blinatumomab antibody formation
Timepoint [6] 0 0
Up to approximately 28 weeks
Secondary outcome [7] 0 0
Dose Expansion Phase: Cmin of blinatumomab
Timepoint [7] 0 0
Up to approximately 28 weeks
Secondary outcome [8] 0 0
Dose Expansion Phase: Cmax of blinatumomab
Timepoint [8] 0 0
Up to approximately 28 weeks
Secondary outcome [9] 0 0
Dose Expansion Phase: Tmax of blinatumomab
Timepoint [9] 0 0
Up to approximately 28 weeks
Secondary outcome [10] 0 0
Dose Expansion Phase: AUC of blinatumomab
Timepoint [10] 0 0
Up to approximately 28 weeks
Secondary outcome [11] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Relapse-Free Survival in participants who achieve CR/CRh within the first 2 cycles(R/R B-ALL)
Timepoint [11] 0 0
Up to 68 days
Secondary outcome [12] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Overall survival (OS)
Timepoint [12] 0 0
Up to approximately 28 weeks
Secondary outcome [13] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Duration of complete response
Timepoint [13] 0 0
Up to approximately 28 weeks
Secondary outcome [14] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more TEAEs
Timepoint [14] 0 0
Up to approximately 28 weeks
Secondary outcome [15] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event
Timepoint [15] 0 0
Up to approximately 28 weeks
Secondary outcome [16] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events
Timepoint [16] 0 0
Up to approximately 28 weeks
Secondary outcome [17] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Number of participants who experience one or more AEs
Timepoint [17] 0 0
Up to approximately 28 weeks
Secondary outcome [18] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)
Timepoint [18] 0 0
Baseline (Day 1) up to approximately 28 weeks
Secondary outcome [19] 0 0
Dose Expansion Phase and Phase 2 (Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30
Timepoint [19] 0 0
Baseline (Day 1) up to approximately 28 weeks

Eligibility
Key inclusion criteria
* Aged 18 years or older.
* Participants with B-precursor ALL with any of the following:

* Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR
* In untreated first, second, third or greater relapse or refractory relapse

* First Relapse is defined as achievement of first Complete Remission (CR) [CR1] during upfront therapy then relapse during or after continuation therapy
* Primary Refractory disease is defined as the absence of CR after standard induction therapy
* Refractory relapse is defined as lack of CR after salvage treatment
* Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
* Refractory to salvage is defined as no attainment of CR after salvage
* Relapsed or Refractory at any time after first salvage therapy.
* Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Greater than or equal to 5% blasts in the Bone Marrow (Exception: Isolated Non-central nervous system (CNS) extramedullary disease [EMD]).
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.

The above is a summary, other inclusion criteria details may apply.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia.
* History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (= grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
* Isolated Extramedullary (EM) Disease
* Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
* Testicular leukemia
* History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
* Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
* Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
* Immunotherapy within 4 weeks before start of protocol-specified therapy. Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed, if treatment ended more than 4 weeks prior to start of protocol therapy therapy and no prior CNS complications.
* Currently receiving treatment in or less than 30 days since ending treatment on another investigational study(ies).
* Abnormal screening laboratory parameters.
* Female participant: Expected to breastfeed during treatment and for 96 hours after the last dose of treatment.

The above is a summary, other exclusion criteria details 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/07/2032
Actual
Sample size
Target
125
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Austin Health, Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
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 York
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
France
State/province [9] 0 0
Nice cedex 3
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
France
State/province [11] 0 0
Toulouse cedex 9
Country [12] 0 0
Germany
State/province [12] 0 0
Augsburg
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Jena
Country [15] 0 0
Germany
State/province [15] 0 0
Koeln
Country [16] 0 0
Germany
State/province [16] 0 0
Leipzig
Country [17] 0 0
Germany
State/province [17] 0 0
Tuebingen
Country [18] 0 0
Germany
State/province [18] 0 0
Ulm
Country [19] 0 0
Italy
State/province [19] 0 0
Bergamo
Country [20] 0 0
Italy
State/province [20] 0 0
Bologna
Country [21] 0 0
Italy
State/province [21] 0 0
Brescia
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Roma
Country [24] 0 0
Japan
State/province [24] 0 0
Akita
Country [25] 0 0
Japan
State/province [25] 0 0
Chiba
Country [26] 0 0
Japan
State/province [26] 0 0
Fukushima
Country [27] 0 0
Japan
State/province [27] 0 0
Kanagawa
Country [28] 0 0
Netherlands
State/province [28] 0 0
Rotterdam
Country [29] 0 0
Spain
State/province [29] 0 0
Andalucía
Country [30] 0 0
Spain
State/province [30] 0 0
Castilla León
Country [31] 0 0
Spain
State/province [31] 0 0
Cataluña
Country [32] 0 0
Spain
State/province [32] 0 0
Comunidad Valenciana
Country [33] 0 0
Spain
State/province [33] 0 0
Navarra
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Turkey
State/province [35] 0 0
Istanbul
Country [36] 0 0
Turkey
State/province [36] 0 0
Izmir

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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
[email protected]
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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04521231