Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000728831
Ethics application status
Approved
Date submitted
19/06/2012
Date registered
6/07/2012
Date last updated
14/03/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of the antiviral drug, Peg-interferon, in patients with relapsed haematological malignancy after initial sibling or volunteer unrelated allogeneic haematopoietic progenitor cell transplantation (HPCT)
Scientific title
A phase I / II study to evaluate the effect of pegylated-Interferon-2alpha on overall survival in patients with relapsed haematological malignancy after allogeneic haematopoietic progenitor cell transplantation (HPCT)
Secondary ID [1] 280656 0
Nil
Universal Trial Number (UTN)
U1111-1131-7551
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haematological relapse (more than or equal to 5 percent blasts) or non-Haematological relapse (molecular, cytogenetic or flow cytometry only) after initial sibling or volunteer unrelated allogeneic HPCT. 286677 0
Condition category
Condition code
Cancer 286980 286980 0 0
Leukaemia - Acute leukaemia
Cancer 287111 287111 0 0
Leukaemia - Chronic leukaemia
Cancer 287172 287172 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pegasys"Registered Trademark" is a recombinant interferon-2alpha protein produced by recombinant DNA technology within E coli and then conjugated to a polyethylene glycol chain (PEG) molecule of 40 kilodaltons. Pegylation of the native IFN molecule eliminates renal excretion and prolongs the drug half-live from 3-4 hours to 160 hours after subcutaneous dosing, reaching steady state in 5-8 weeks. For this reason pegylation of IFN results in prolonged action and avoids the need for the daily dosing required for the native cytokine and the frequent peak and troughs seen therein. In general pegylation of cytokines result in significantly prolonged activity and enhanced potency in vivo.
Pegasys"Registered Trademark" will commence at a dose of 45mcg subcutaneously once per week, with weekly escalation of dose to 90mcg, then 135mcg then 180mcg if tolerated. Patients will then continue peg-IFN as “maintenance” at 180mcg weekly for a total of 6 months (calculated from first dose of peg-IFN) if able.

Importantly, the administration of pegylated-IFN after allogeneic BMT has not been studied previously.
Intervention code [1] 285064 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] 287315 0
The primary endpoint is overall survival
Timepoint [1] 287315 0
2 years
Secondary outcome [1] 297889 0
Disease Response assessed by bone marrow aspirate
Timepoint [1] 297889 0
2 years
Secondary outcome [2] 297892 0
Incidence of Graft Versus Host Disease (GVHD) assessed using acute and chronic Seattle assessment criteria
Timepoint [2] 297892 0
2 years
Secondary outcome [3] 297893 0
Treatment related mortality and peg-IFN related toxicity by medical assessment and blood tests
Timepoint [3] 297893 0
2 years

Eligibility
Key inclusion criteria
*Patients with relapse of their primary disease after allogeneic HPCT (either sibling or VUD donors).
*Age greater than or equal to 18 years and less than 70 years
*Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >50%)
*Off immune suppression:
Patients are allowed to continue on prednisolone (or equivalent) at doses <0.5mg/kg/day.
Patients must have ceased Cyclosporine (CSA), Tacrolimus (Tacro), Mycophenolate Mofetil (MMF) and / or all other immunosuppressants
*Absence of active significant graft versus host disease off immunosupression defined by less than grade 2 acute graft vesus host disease and or progressive or extensive stage chronic graft versus host disease.
*Adequate organ function for FLAG chemotherapy:
Total Bilirubin less than or equal to 30umol/L
Creatinine clearance less than or equal to 50ml/min/1.73m^2 for patients with creatinine levels above ULN
Minimum age
18 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Inadequate organ function for FLAG chemotherapy (if in haematological relapse):
Total Bilirubin >30umol/L
Creatinine Clearance < 50ml/min/1.73m^2 for patients with creatinine levels above ULN
*Active acute (grade II-IV) or progressive and / or extensive stage chronic GVHD requiring immune suppression with prednisone (or equivalent) at doses >0.5mg/kg/day or ongoing therapy with other immunosuppressant medications including calcineurin inhibitors (cyclosporine, Tacrolimus) and MMF.
*Patients receiving any other investigational agents
*Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, uncontrolled hypertension or heart failure, uncontrolled diabetes, uncontrolled autoimmune disease (especially thyroid), uncontrolled COPD, uncontrolled depression, epilepsy and social situations that would limit compliance with study requirements.
*Known HIV infection.
*Pregnant or breastfeeding, or patient with reproductive potential who is not willing to use adequate contraceptive precautions in the judgement of the Investigator. Adequate contraception is defined as a double-barrier method, i.e. using at least 2 methods of contraception e.g. 2 actual barrier methods or 1 actual barrier method and 1 hormonal method.
*Donor is an identical twin (i.e. syngeneic)
*History of allergic or grade IV reactions to interferon, including known allergies to E coli-derived products eg. G-CSF.

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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/06/2012
Actual
4/07/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 285444 0
Government body
Name [1] 285444 0
Queensland Health Senior Clinical Research Fellowship to CI Hill
Country [1] 285444 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] 284291 0
Other
Name [1] 284291 0
Queensland Institute of Medical Research
Address [1] 284291 0
Clive Berghofer Cancer Research Centre
Herston Road,
Herston. 4006
QLD.
Country [1] 284291 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294614 0
Royal Brisbane & Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 294614 0
Butterfield Street,
Herston. 4006
Queensland
Ethics committee country [1] 294614 0
Australia
Date submitted for ethics approval [1] 294614 0
21/06/2012
Approval date [1] 294614 0
14/08/2012
Ethics approval number [1] 294614 0

Summary
Brief summary
There are no standard approaches to treat haematological malignancies that relapse after allogeneic HPCT. This trial aims to evaluate the safety and efficacy of treatment with the anti-viral drug, Peg-Interferon, in patients with relapsed haematological malignancy after allogeneic haematopoietic progenitor cell transplantation (HPCT).
Who is it for?
You may be eligible to join this study if you are aged between 18 and 65 years old.
Trial details
Patients will initially have their immunosuppression withdrawn, and in the presence of frank haematological relapse, also undertake FLAG induction chemotherapy as a platform to provide both short-term disease control as well as lymphodepletion. In the absence of development of subsequent GVHD, Peg-Interferon will commence at a dose of 45mcg subcutaneouly once per week, with weekly escalation of dose to 90mcg, then 135mcg then 180mcg if tolerated. Patients will then continue peg-IFN as “maintenance” at 180mcg weekly for a total of 6 months (calculated from first dose of peg-IFN) if able. If after achieving maximal doses of pegylated-IFN (180mcg/week) significant GVHD has not developed, depending on donor availability, patients will also be eligible to commence donor lymphocyte infusions (DLI) whilst continuing pegylated-IFN.
This approach will (i) permit the use of chemotherapy without the induction of severe GVHD that is seen in the majority of patients that receive a second stem cell graft (ii) whilst permitting peg-IFN to be delivered to the majority of recipients and (iii) allowing DLI to be administered thereafter to poor responders.
Participants will be assessed at 2 years following enrolment to determine how they responded to this treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34300 0
Prof Geoff Hill
Address 34300 0
Queensland Institute of Medical Research clive Berghofer cancer Research Centre Herston Road, Herston. 4029 QLD
Country 34300 0
Australia
Phone 34300 0
+61 7 38453763
Fax 34300 0
Email 34300 0
[email protected]
Contact person for public queries
Name 17547 0
A/Prof Glen Kennedy
Address 17547 0
Royal Brisbane and Women's Hospital
Cancer Care Services
Level 5 Joyce Tweddell Building
Butterfield Street,
Herston. 4029
QLD
Country 17547 0
Australia
Phone 17547 0
+61 7 36461340
Fax 17547 0
+61 7 36467371
Email 17547 0
[email protected]
Contact person for scientific queries
Name 8475 0
Prof Geoff Hill
Address 8475 0
Queensland Institute of Medical Research
clive Berghofer cancer Research Centre
Herston Road,
Herston. 4029
QLD
Country 8475 0
Australia
Phone 8475 0
+61 7 38453763
Fax 8475 0
+61 7 38453509
Email 8475 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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