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Trial registered on ANZCTR


Registration number
ACTRN12619000581167
Ethics application status
Approved
Date submitted
28/03/2019
Date registered
15/04/2019
Date last updated
15/04/2019
Date data sharing statement initially provided
15/04/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Brentuximab Vedotin in combination with donor lymphocyte infusions for Hodgkin lymphoma relapsing or persisting after allogeneic stem cell transplantation
Scientific title
Efficacy of Positron Emission Tomography (PET) directed combination therapy with Brentuximab Vedotin and donor lymphocyte infusion in Hodgkin lymphoma relapsing or persisting after allogeneic haematopoietic stem cell transplantation
Secondary ID [1] 297832 0
None
Universal Trial Number (UTN)
Trial acronym
Brentuximab-DLI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin lymphoma 312202 0
Condition category
Condition code
Cancer 310746 310746 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo a positron-emission tomography (PET) scan 60 days after allogeneic transplantation, and 3 monthly thereafter for 24 months.

Demonstration of persisting or relapsed Hodgkin lymphoma on PET scan after transplantation will initiate commencement of Brentuximab vedotin 1.8mg/kg by intravenous infusion every 3 weeks. Persisting or relapsed Hodgkin lymphoma will be defined as Deauville score 4 or 5, not attributed to other causes eg. infection or inflammation. Where possible, persisting or relapsed Hodgkin lymphoma on PET will be confirmed by tissue biopsy.

After 3 doses of brentuximab (ie. 9 weeks), donor lymphocyte infusions will be administered by intravenous infusion commencing at an initial dose of 1x10^6 CD3+ cells/kg, escalating in graded increments to a maximum of 100x10^6 CD3+ cells/kg. DLI will be administered once every 3 weeks until a maximum of 100x10^6 CD3+ cells/kg are administered or until grade 2-4 acute GVHD develops.

Increments of DLI will be:
1x10^6 CD3+ cells/kg
5x10^6 CD3+ cells/kg
10x10^6 CD3+ cells/kg
50x10^6 CD3+ cells/kg
100x10^6 CD3+ cells/kg

Intervention fidelity will not be assessed in this study.
Intervention code [1] 314069 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319595 0
Overall response rate (complete and partial response) assessed by PET scan.
Timepoint [1] 319595 0
18 weeks after initiation of Brentuximab
Secondary outcome [1] 368820 0
Composite outcome of grade 2-4 acute GVHD or moderate to severe chronic GVHD

Acute GVHD will be assessed by Glucksberg criteria
Chronic GVHD will be assessed by NIH criteria
Timepoint [1] 368820 0
18 weeks after commencement of Brentuximab

Eligibility
Key inclusion criteria
Each participant must meet all the following criteria:
1. Age 18 years or older
2. Have a diagnosis of CD30+ Hodgkin lymphoma in any remission status
3. Undergoing or less than 60 days post-alloHCT from a matched related or unrelated adult donor

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting any of the following exclusion criteria (at time of screening) are not to be enrolled in the study:
1. Prior exposure to brentuximab vedotin with less than PR or hypersensitivity reaction manifesting with anaphylaxis, Stevens-Johnson syndrome or toxic epidermal necrolysis or any adverse reaction attributed to brentuximab vedotin with severity greater than or equal to grade 2
2. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
3. Any sensory or motor peripheral neuropathy greater than or equal to grade 2
4. Known cerebral or meninteal disease (Hodgkin lymphoma or any other aetiology) including signs or symptoms of progressive multifocal leukoencephalopathy
5. Knwon hepatitis B surface antigen positive, or known or suspected actuve hepatitis C infection
6. Knwon human immunodeficiency virus (HIV) exposure
7. Diagnosed or treated for another malignancy within 3 years before the first dose or previoiusly diagnosed with anther malignancy and have evidence of residual disease
8. Known history of any of the following cardiovascular conditions: myocardial infarction within 2 years of registration; class III or IV heart failure; evidence of uncontrolled cardovascular conditions; left venticular ejection fraction <50%

9. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
10. Paatients that have had prior chemotherapy or other investigational agents within 5 half-lives of the last dose of that treatment
11. Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on day 1 before first dose of study drug

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 13517 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 26136 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 302354 0
Commercial sector/Industry
Name [1] 302354 0
Millenium Pharmaceuticals
Address [1] 302354 0
40 Landsdowne Street
Cambrige, Massachusetts
USA 02139
Country [1] 302354 0
United States of America
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Royal Melbourne Hospital
Grattan Street
Parkville, Victoria 3050
Country
Australia
Secondary sponsor category [1] 302241 0
None
Name [1] 302241 0
Address [1] 302241 0
Country [1] 302241 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303028 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 303028 0
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Ethics committee country [1] 303028 0
Australia
Date submitted for ethics approval [1] 303028 0
Approval date [1] 303028 0
25/11/2016
Ethics approval number [1] 303028 0

Summary
Brief summary
This study investigates the effectiveness and safety of the combination of Brentuximab vedotin and donor lymphocyte infusions for Hodgkin lymphoma that has relapsed or persists after an allogeneic stem cell transplant.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with CD30+ Hodgkin lymphoma in any remission status, for which you are undergoing allogeneic hematopoietic cell transplantation (alloHCT) OR are less than or equal to 60 days post-alloHCT from a matched related or unrelated adult donor.

Study details
All participants in this study will be monitored for relapse of Hodgkin lymphoma by positron emission tomography (PET) scans commencing 60 days after allogeneic transplant, and then 3 monthly thereafter. Upon identification of relapse of Hodgkin lymphoma, patients will receive treatment with brentuximab 1.8mg/kg every 3 weeks intravenously. After 3 doses of brentuximab, patients will also commence donor lymphocyte infusions at an initial dose of 1x10^6 T cells/kg intravenously, escalating to a maximum of 1x10^8 T cells/kg in a graded fashion. Donor lymphocyte infusions will be administered once every 3 weeks for a total of up to 5 infusions.

Participants will undergo PET scans to assess response every 3 months for 24 months.

This research will examine the effectiveness of treatment with the combination of brentuximab vedotin and donor lymphocyte infusions, which may be an important strategy for patients with Hodgkin lymphoma that relapses after allogeneic transplant.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92222 0
Prof David Ritchie
Address 92222 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92222 0
Australia
Phone 92222 0
+61 3 93427000
Fax 92222 0
Email 92222 0
david.ritchie@mh.org.au
Contact person for public queries
Name 92223 0
Prof David Ritchie
Address 92223 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92223 0
Australia
Phone 92223 0
+61 3 93427000
Fax 92223 0
Email 92223 0
david.ritchie@mh.org.au
Contact person for scientific queries
Name 92224 0
Prof David Ritchie
Address 92224 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92224 0
Australia
Phone 92224 0
+61 3 93427000
Fax 92224 0
Email 92224 0
david.ritchie@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will remain confidential.
What supporting documents are/will be available?
Study protocol
Informed consent form
Clinical study report
Ethical approval
Summary results
No Results