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Trial registered on ANZCTR


Registration number
ACTRN12611000015943
Ethics application status
Approved
Date submitted
16/12/2010
Date registered
6/01/2011
Date last updated
6/01/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Triple therapy for primary immune thrombocytopenia
Scientific title
Efficacy, safety and tolerability of combination therapy with high dose dexamethasone, low dose rituximab and cyclosporine in patients with primary immune thrombocytopenic purpura (ITP)
Secondary ID [1] 253306 0
HREC/10/STG/59
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary immune thrombocytopenia 258839 0
Condition category
Condition code
Blood 258978 258978 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
triple therapy:
1. high dose dexamethasone (40mg orally days 1-4)
2. low dose rituximab (fixed 100mg intravenous days 7, 14, 21, 28)
3. cyclosporine (2.5-3mg/kg/day orally in 2 divided doses days 1-28)

overall duration of treatment is 1 cycle of therapy.
Intervention code [1] 257757 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259832 0
Response rate (platelet count >30x10^9/L, at least 2 fold increase in baseline platelet count and absence of bleeding)
Timepoint [1] 259832 0
6 months
Primary outcome [2] 259833 0
Complete response rate (platelet count >100x10^9/L, at least 2 fold increase in platelet count and absence of bleeding)
Timepoint [2] 259833 0
6 months
Secondary outcome [1] 268678 0
Tolerability of triple therapy (assessed using standardised questions for common adverse effects seen in patients taking these drugs, graded according to CTCAE version 4.0)
Timepoint [1] 268678 0
24 months
Secondary outcome [2] 268679 0
Safety of triple therapy (assessed using standardised questions for common adverse effects seen in patients taking these drugs, graded according to CTCAE version 4.0 and documentation of all unexpected events while under study observation)
Timepoint [2] 268679 0
24 months
Secondary outcome [3] 268680 0
Response rate (platelet count >30x10^9/L, at least 2 fold increase in baseline platelet count and absence of bleeding)
Timepoint [3] 268680 0
12 months
Secondary outcome [4] 268681 0
Response rate (platelet count >30x10^9/L, at least 2 fold increase in baseline platelet count and absence of bleeding)
Timepoint [4] 268681 0
24 months
Secondary outcome [5] 268682 0
Complete response rate (platelet count >100x10^9/L, at least 2 fold increase in platelet count and absence of bleeding)
Timepoint [5] 268682 0
12 months
Secondary outcome [6] 268683 0
Complete response rate (platelet count >100x10^9/L, at least 2 fold increase in platelet count and absence of bleeding)
Timepoint [6] 268683 0
24 months
Secondary outcome [7] 268684 0
Sustained response rate (platelet count >50x10^9/L and absence of bleeding)
Timepoint [7] 268684 0
6 months
Secondary outcome [8] 268685 0
Initial response rate (platelet count >50x10^9/L and absence of bleeding)
Timepoint [8] 268685 0
30 days
Secondary outcome [9] 268686 0
Time to platelet count response
Timepoint [9] 268686 0
weekly for 4 weeks then monthly for 24 months
Secondary outcome [10] 268687 0
Demonstration of successful lymphocyte depletion with low-dose rituximab
Timepoint [10] 268687 0
monthly for 24 months

Eligibility
Key inclusion criteria
Primary ITP as diagnosed according to IWG guidelines (Provan et, 2010)
Platelet count <30x10^9/L or 30-50x10^9/L with either 1. evidence of ongoing bleeding secondary to thrombocytopenia or 2. treatment dependence including corticosteroids, IVIG, second-line immunosuppressants and TPO-agonists.
Fully informed written consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Treatment in the last 6 months with combination therapy of high dose corticosteroids (methylprednisolone >30mg/kg/day for 3 days or high dose dexamethasone 40mg/day for 4 days) and either anti-CD 20 antibody (rituximab) or anti-T cell therapy with cyclosporine or mycophenolate mofetil
Active malignant disease - except BCC or SCC of skin
Untreated hepatitis B infection
Active opportunistic infection or untreated tuberculosis
Life expectancy of less than 12 months
Moderate-severe renal impairment (eGFR<50mL/min)
Poorly controlled hypertension (BP>140/80)
Pregnancy in females of child-bearing age

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)
Open-label study
Patients enrolled by invitation of treating physician in collaboration with investigators
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Nil
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
Recruitment postcode(s) [1] 3515 0
2217

Funding & Sponsors
Funding source category [1] 258224 0
Hospital
Name [1] 258224 0
St George Hospital
Address [1] 258224 0
Gray Street, Kogarah, NSW 2217
Country [1] 258224 0
Australia
Primary sponsor type
Individual
Name
Professor Beng Hock Chong
Address
Level 2 Pitney Building
St George Clinical School, Medicine
University of New South Wales
Gray Street
St George Hospital, Kogarah, NSW 2217
Country
Australia
Secondary sponsor category [1] 257392 0
None
Name [1] 257392 0
Address [1] 257392 0
Country [1] 257392 0
Other collaborator category [1] 251744 0
Individual
Name [1] 251744 0
Dr Philip Young-Ill Choi
Address [1] 251744 0
Level 2 Pitney Building
St George Clinical School, Medicine
University of New South Wales
Gray Street
St George Hospital, Kogarah, NSW 2217
Country [1] 251744 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260206 0
South Eastern Sydney and Illawarra Area Health Service Human Research Ethics Committee - Central Network
Ethics committee address [1] 260206 0
Research Management Office
Level 3, James Laws House
St George Hospital
Gray Street, Kogarah NSW 2217
Ethics committee country [1] 260206 0
Australia
Date submitted for ethics approval [1] 260206 0
08/06/2010
Approval date [1] 260206 0
03/11/2010
Ethics approval number [1] 260206 0
HREC/10/STG/59

Summary
Brief summary
As the major immune cell types involved in initiating and sustaining the ITP disease are antigent presenting cells (APC), B cells and T cells (Chong 2009, Kuwana 2009), it is reasonable to expect better long-term response rates by using drugs targeting all three cell types: namely an anti-B cell agent (rituximab), an anti-APC drug (high dose dexamethasone) and an anti-T cell treatment (cyclosporine).

By combining these drugs together over a short period of time (4 weeks), we hope to maximise the efficacy while minimising anticipated toxicities associated with longer-term use of these drugs.
Trial website
none
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 32023 0
Address 32023 0
Country 32023 0
Phone 32023 0
Fax 32023 0
Email 32023 0
Contact person for public queries
Name 15270 0
Dr Philip Choi
Address 15270 0
Level 2, Pitney Building
St George Clinical School, Medicine, UNSW
Gray Street, Kogarah NSW 2217
Country 15270 0
Australia
Phone 15270 0
+61291133851
Fax 15270 0
+61291133958
Email 15270 0
z2172099@unsw.edu.au
Contact person for scientific queries
Name 6198 0
Dr Philip Choi
Address 6198 0
Level 2, Pitney Building
St George Clinical School, Medicine, UNSW
Gray Street, Kogarah NSW 2217
Country 6198 0
Australia
Phone 6198 0
+61291133851
Fax 6198 0
+61291133958
Email 6198 0
z2172099@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results