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Trial registered on ANZCTR


Registration number
ACTRN12606000326594
Ethics application status
Not required
Date submitted
28/06/2006
Date registered
31/07/2006
Date last updated
18/06/2021
Date data sharing statement initially provided
18/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Prospective study of Rituximab for chronic graft vs host disease (GVHD) sub-optimally responsive to immunosuppressive therapy: Assessment of response.
Scientific title
Prospective study of Rituximab for chronic graft vs host disease (GVHD) sub-optimally responsive to immunosuppressive therapy: Assessment of response.
Secondary ID [1] 286 0
Australasian Leukaemia and Lymphoma Group (ALLG): ALLG BM09
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic graft versus host disease post allogeneic bone marrow transplant 1296 0
Condition category
Condition code
Surgery 1386 1386 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive one course of Rituximab induction therapy, consisting of four intravenous infusions of Rituximab, each of them one week apart. Further clinical trial procedures depend on the response of the cGVHD at 3 months after completion of Rituximab induction therapy. For patients who are eligible to remain in the study these further trial procedures may consist of a follow-up period without further Rituximab administration or Rituximab reinduction therapy (comparable to the induction therapy), possibly (depending on the response of cGVHD) followed by a Rituximab maintenance therapy consisting of four intravenous infusions of Rituximab, each of them 3 months apart. Total follow up will be up to a maximum of 3.5 years.
Intervention code [1] 1178 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 1890 0
The overall response (partial response [PR] and complete response [CR]) of patients with cGVHD assessed either by the criteria according to the staging proposal of the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease or by reduction in immunosuppressive therapy
Timepoint [1] 1890 0
At 3 months after completion of Rituximab induction therapy
Secondary outcome [1] 3334 0
1. The response (PR and CR) to Rituximab in different subtypes of cGVHD (sclerodermatous cGVHD/other cGVHD).
Timepoint [1] 3334 0
At 3 months after completion of Rituximab induction therapy.
Secondary outcome [2] 3335 0
2. The response (PR and CR) at 6 and 12 months after completion of Rituximab induction therapy, in the absence of Rituximab reinduction therapy, in patients who present with PR or CR.
Timepoint [2] 3335 0
At 3 months after completion of Rituximab induction therapy.
Secondary outcome [3] 3336 0
3. The incidence of Rituximab reinduction therapy determined at 12 months after end of Rituximab induction therapy in patients who present with PR or CR.
Timepoint [3] 3336 0
At 3 months after completion of Rituximab induction therapy.
Secondary outcome [4] 3337 0
4. The response (PR and CR) to Rituximab at 3, 6, 12, 18 and 24 months after completion of Rituximab reinduction therapy in patients who present with PR or CR at 3 months after completion of Rituximab induction therapy (noting that Rituximab maintenance therapy will be given at 3, 6, 9 and 12 months after completion of Rituximab reinduction therapy to patients who present with PR or CR at 3 months after end of Rituximab reinduction therapy)
Timepoint [4] 3337 0
Secondary outcome [5] 3338 0
5. Relapse free survival with respect to permanent reduced/discontinued immunosuppressive therapy and with respect to permanent reduction of cGVHD symptoms in patients who present with PR or CR.
Timepoint [5] 3338 0
At 3 months after completion of Rituximab induction therapy.
Secondary outcome [6] 3339 0
6. Death from non-relapse causes after application of Rituximab
Timepoint [6] 3339 0
Secondary outcome [7] 3340 0
7. Primary treatment failure.
Timepoint [7] 3340 0
At 3 months after end of Rituximab induction therapy.
Secondary outcome [8] 3341 0
8. The response (PR and CR) to Rituximab at 3, 6, 12, 18 and 24 months after completion of Rituximab reinduction therapy in patients who present at 3 months after completion of Rituximab induction therapy with MR or NR after initial PR or CR (noting that Rituximab maintenance therapy will be given at 3, 6, 9 and 12 months after completion of Rituximab reinduction therapy to patients who present with PR or CR at 3 months after end of Rituximab reinduction therapy
Timepoint [8] 3341 0
Secondary outcome [9] 3342 0
9. The impact of the treatment on the subject reported outcomes.
Timepoint [9] 3342 0
Secondary outcome [10] 3343 0
10. The safety of Rituximab application
Timepoint [10] 3343 0

Eligibility
Key inclusion criteria
1. Severe chronic Graft Versus Host Disease (cGVHD) diagnosed according to the NIH staging proposal irrespective of the site affected, e.g. (but not restricted to): cutaneous/subcutaneous, hepatic, renal, pulmonary, conjunctival, oral, vaginal, musculoskeletal or haematological cGVHD. 2. Severe cGVHD meeting any of the following 3 criteria:a) failing response during therapy of 2 weeks of greater than or equal to 1 mg/kg prednisolone per day or relapse of symptoms when tapering prednisolone to doses of greater than or equal to 0.5 mg/kg b) suboptimal response to a minimum of two months of at least two immunosuppressants c) clinically significant relapse of cGVHD within 3 months of cessation of immunosuppression for the initial episode of cGVHD OR second relapse (with all three episodes occurring within 18 months). 3. Patients with long-standing cGVHD (defined as >6 months of accumulated intensive therapy, as defined above under 1. and 2.) are only eligible if there is unequivocal biopsy proof of ongoing active inflammation (e.g. lymphocytic infiltrate with cellular damage) in the relevant organ e.g. skin. 4. ECOG performance status < grade 2 and life expectancy > 3 months. 5. Signed written informed consent to participate in the study.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with “burnt-out” cGVHD, i.e. long-standing cGVHD who lack an unequivocal biopsy proof of ongoing active inflammation (e.g. lymphocytic infiltrate with cellular damage) in the relevant organ e.g. skin.2. Secondary tumour, other than basal cell carcinoma, after allogeneic transplantation3. Presence of an EBV-associated post transplant lymphoproliferative disease4. Severe uncontrolled infections (note: treated CMV-reactivation, resolved sepsis, responsive fungal infection will not be exclusion criteria)5. Uncontrolled relapse of the original haematological condition for which the transplant was performed6. Pregnancy or breast feeding7. ECOG performance status grade 3 to 4 or expected life expectancy <3 months8. Concurrent or previous therapy with Rituximab (except application before transplantation for control of CD20+ malignancy)9. Hypersensitivity against Rituximab or other human immunoglobulin preparations10. Concurrent participation in another investigative drug trial11. Inability to understand the nature and the extent of the trial and the procedures required.

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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Subject to verification
Date of first participant enrolment
Anticipated
1/09/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 1520 0
Commercial sector/Industry
Name [1] 1520 0
Roche Australia
Country [1] 1520 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
35 Elizabeth St, Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 1335 0
None
Name [1] 1335 0
nil
Address [1] 1335 0
Country [1] 1335 0

Ethics approval
Ethics application status
Not required

Summary
Brief summary
Chronic graft vs host disease (cGVHD) can affect a number of target organs following bone marrow transplantation. In such cases, numerous combinations of immunosuppressive drugs are used to try and control the cGVHD. Often these drugs are not particularly successful yet patients may need to remain on quite intensive immunosuppressant therapy in the long term. The aim of this study is to see whether the drug rituximab (also called mabthera) is effective in improving cGVHD in these patients so that the dose of immunosuppressant drugs can be reduced. Rituximab reduces the number of a type of white cell called B lymphocytes which may be over active in patients with cGVHD. Small studies overseas have shown that some patients with GVHD have responded very well to rituximab. This study is designed to treat a larger number of patients so we can more clearly define the value of this treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35327 0
A/Prof Andrew Grigg
Address 35327 0
Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050. Australia
Country 35327 0
Australia
Phone 35327 0
+61 3 93427619
Fax 35327 0
+61 3 94328022
Email 35327 0
[email protected]
Contact person for public queries
Name 10367 0
Peter Shuttleworth
Address 10367 0
BMT Service, Royal Melbourne Hospital, Parkville, VIC 3050
Country 10367 0
Australia
Phone 10367 0
03-9342 8198
Fax 10367 0
03-9342 8198
Email 10367 0
[email protected]
Contact person for scientific queries
Name 1295 0
Associate Professor Andrew Grigg
Address 1295 0
BMT Service, Royal Melbourne Hospital, Parkville, Vic 3050
Country 1295 0
Australia
Phone 1295 0
03-9342 7690
Fax 1295 0
03-9342 8022
Email 1295 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.