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Trial registered on ANZCTR


Registration number
ACTRN12613000288729
Ethics application status
Approved
Date submitted
25/09/2012
Date registered
13/03/2013
Date last updated
17/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Substituting the drug, alemtuzumab, for another drug known as ATGAM (Antithymocyte Globulin - equine), as part of combination therapy for steroid-refractory acute graft versus host disease in post haematopoietic progenitor cell transplantation patients.
Scientific title
Substitution of alemtuzumab for ATGAM (Antithymocyte Globulin - equine) as part of combination therapy including etanercept, tacrolimus and mycophenolate mofetil for steroid-refractory acute graft versus hosts disease (SR-GVHD) post haematopoietic progenitor cell transplantation (HPCT): evaluation of treatment response and survival at 6 months
Secondary ID [1] 281290 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Steroid refractory acute graft versus host disease post haematopoietic progenitor cell transplantation. 287500 0
Condition category
Condition code
Cancer 287824 287824 0 0
Leukaemia - Acute leukaemia
Cancer 287825 287825 0 0
Leukaemia - Chronic leukaemia
Cancer 287826 287826 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Alemtuzumab given for 5 consecutive days, in 250 mls of Normal Saline over 2 hours. Dose is fixed at 5mg IV per day in all patients, irrespective of weight. All patients will recieve standard premedication with two paracetamol orally, phenergen 12.5mg intravenously and hydrocortisone 100mg intravenously 30 minutes prior to alemtuzumab.
Intervention code [1] 286715 0
Treatment: Drugs
Comparator / control treatment
Single group trial. the same intervention is applied to all subjects in the study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288047 0
Overall survival post commencement of alemtuzumab
Timepoint [1] 288047 0
6 months
Secondary outcome [1] 299332 0
Response to salvage therapy: including complete response, partial response rate, and overall response rate assessed by medical assessment and using acute and chronic Seattle assessment criteria.
Timepoint [1] 299332 0
6 months post commencement of alemtuzumab
Secondary outcome [2] 299333 0
Infection rate assessed by medical assessment and blood tests
Timepoint [2] 299333 0
6 months post commencement of alemtuzumab
Secondary outcome [3] 299334 0
Incidence of chronic Graft versus Host Disease (GVHD) assessed using chronic Seattle assessment criteria
Timepoint [3] 299334 0
6 months post commencement of alemtuzumab
Secondary outcome [4] 299418 0
Plasma cytokine levels before and after Alemtuzumab therapy assessed by blood tests
Timepoint [4] 299418 0
6 months post commencement of alemtuzumab
Secondary outcome [5] 299419 0
Kinetics of antigen presenting cell and donor T cell reconstitution following depletion by alemtuzumab in peripheral blood assessed by blood tests
Timepoint [5] 299419 0
6 months post commencement of alemtuzumab

Eligibility
Key inclusion criteria
*Age greater than18 and less than 70 years
*Patients must suffer SR-GVHD, as defined by:

#Progressive disease (i.e any new organ involvement and/or worsening by greater than or equal to 1 grade of GVHD) after 3 days of therapy with prednisolone (or equivalent) at greater than or equal to 1mg/kg/day, and / or

#No change in GVHD grade after 7 days of therapy with prednisolone (or equivalent) at greater than 1mg/kg/day, and / or

#Incomplete response (i.e less than CR) after 14 days of primary therapy with prednisolone (or equivalent) at greater than 1mg/kg/day and / or

#Recurrence of GVHD (greater than grade 1) on steroid taper while receiving grater than 0.5mg/kg of prednisolone (or equivalent) per day.

#GVHD diagnosis must be proven by histological assessment of target organ biopsy.

#GVHD grade must be greater than II as per Glucksberg criteria.

#Ability to understand and the willingness to sign a written informed consent document.
Minimum age
18 Years
Maximum age
69 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Patients receiving any other investigational agents.

*Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

*HIV, HCV and HBV infection.

*Pregnancy, or refusal to use adequate contraception to prevent pregnancy.

*History of allergic reactions attributed to compounds of similar chemical or biologic composition as alemtuzumab or other agents used in the study.

*Patients with known human anti-mouse antibodies (HAMA).

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
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Alemtuzumab was withdrawn from the market for blood cancer therapy and further supply was unable to be obtained in order to complete the study
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)
QLD
Recruitment hospital [1] 7510 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 15334 0
4006 - Bowen Hills

Funding & Sponsors
Funding source category [1] 286054 0
Government body
Name [1] 286054 0
Queensland Health Senior Clinical Research Fellowship to CI Hill
Address [1] 286054 0
Queensland Health Building
147-163 Charlotte Street
Brisbane Queensland 4000
Country [1] 286054 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Womens Hospital
Address
Butterfield Street
Herston. 4006
Brisbane
QLD
Country
Australia
Secondary sponsor category [1] 284867 0
Other
Name [1] 284867 0
Queensland Institute of Medical Research
Address [1] 284867 0
Clive Berghofer Cancer Research Centre
Herston Road
Herston. 4006
QLD
Country [1] 284867 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296977 0
Royal Brisbane and Women'sHospital
Ethics committee address [1] 296977 0
Butterfield Street,
Herston.
Ethics committee country [1] 296977 0
Australia
Date submitted for ethics approval [1] 296977 0
22/06/2012
Approval date [1] 296977 0
14/08/2012
Ethics approval number [1] 296977 0

Summary
Brief summary
The study is evaluating the efficacy of substituting the drug, alemtuzumab, for another drug known as ATGAM, as part of combination therapy for steroid-refractory acute graft versus host disease in post haematopoietic progenitor cell transplantation patients. Who is it for? You may be eligible to join this study if you are a male or female aged between 18-69 years who has been diagnosed with grade II or higher steroid-refractory acute graft versus host disease (SR-GVHD) following haematopoietic progenitor cell transplantation (HPCT). Trial details All participants in this trial will be given the drug alemtuzumab for 5 consecutive days. Alemtuzumab will be administered intravenously (into the vein) over a period of 2 hours each day. All patients will also receive standard premedication (including paracetamol, phenergan and hydrocortisone) 30 minutes prior to alemtuzumab. Participants will be assessed at 6 months in order to evaluate response to treatment and survival.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34748 0
Prof Geoff Hill
Address 34748 0
Queensland Institute of Medical Research
Clive Berghofer Cancer Research Centre
Herston Road
Herston. 4029
QLD
Country 34748 0
Australia
Phone 34748 0
+61 7 38453763
Fax 34748 0
Email 34748 0
Geoff.Hill@qimr.edu.au
Contact person for public queries
Name 17995 0
A/Prof A/Prof Glen Kennedy
Address 17995 0
Royal Brisbane and Women's Hospital
Cancer Care Services
Level 5 Joyce Tweddell Building
Butterfield /street,
Herston. 4029
QLD
Country 17995 0
Australia
Phone 17995 0
+61 7 36461340
Fax 17995 0
+61 7 36467371
Email 17995 0
Glen_Kennedy@health.qld.gov.au
Contact person for scientific queries
Name 8923 0
Prof Prof Geoff Hill
Address 8923 0
Queensland Institute of Medical Research
Clive Berghofer Cancer Research Centre
Herston Road
Herston. 4029
QLD
Country 8923 0
Australia
Phone 8923 0
+61 7 38453763
Fax 8923 0
+61 7 38453509
Email 8923 0
Geoff.Hill@qimr.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary