To improve response rate of primary treatment of extensive chronic GvHD with the addition of MPA to the reference treatment CsA+PDN (comparator)Primary ObjectiveTo improve remission rates with cyclosporine A+ prednisone + Myfortic® (CsA+PDN+MPA)…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
allogene hematopoetische stamceltransplantatie bij diverse maligniteiten
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for the determination of sample size is the response
evaluated 1 year after the inclusion. A sample of 332 patients is estimated,
based on the ability to detect an improvement of the response at 12 months from
an anticipated 60% in the control arm (CsA +PDN) to 75% in the experimental arm
(CsA+PDN+ Myfortic®) with a significant level of 5% and a 80% power.
However, due to potent GvHD-linked infectious death, it has been estimate that
the number of patient per arm will be targeted to 200 (total number 400).
Efficacy success is defined as the response rate (CR+PR) at 12 months post
randomisation, with no secondary systemic therapy (defined below) at any time.
Death or dropout with lack of follow-up information after response of chronic
GvHD but before the final analysis is expected to occur infrequently and will
not be used to negate categorization as efficacy success for purposes of this
study, since the treatment had been effective in controlling chronic GvHD.
It is possible that systemic immunosuppressive treatment will be discontinued
before resolution of all reversible manifestations of chronic GvHD in some
patients. Topical therapy may be continued in this situation, at the discretion
of the managing physician.
Discontinuation of immunosuppressive medications for the purpose of inducing an
anti-tumor response after the development of recurrent or secondary malignancy
will not be categorized as efficacy success.
Secondary outcome
-
Background summary
CsA+PDN remains the gold standard 1st line therapy of chronic GvHD, the most
frequent long-term complication of allogeneic stem cell transplantation.
However, CsA+PDN lead to objective response in only 60% of the patients (at
most) and steroid-induced side effects, including life threatening infections,
are of major concern.
Mycophenolate mofetil (MMF) is currently the second drug used in the treatment
of chronic GvHD and results of few phase II trials suggest its efficacy. A
randomised trial testing improved response with the addition of MPA to CsA+PDN
is timely and warranted.
Study objective
To improve response rate of primary treatment of extensive chronic GvHD with
the addition of MPA to the reference treatment CsA+PDN (comparator)
Primary Objective
To improve remission rates with cyclosporine A+ prednisone + Myfortic®
(CsA+PDN+MPA) combination as compared to the reference treatment with CsA+PDN
Secondary Objectives
• To spare patients from long-term use of corticosteroids (and of their
long-term side effects)
• To decrease transplant-related morbidity (infectious and noninfectious)
• To study time to cessation of any immunosuppressive therapy
• To test prospectively the NIH severity index for chronic GvHD
Study design
Multicentre, randomised placebo-controlled clinical trial
Intervention
Patients are randomised between the following two treatment arms:
ARM A: Cyclosporine A (3mg/kg/D) + prednisone 1.5 mg/kg/D + Placebo BID
ARM B: Cyclosporine A (3mg/kg/D) + prednisone 1.5 mg/kg/D + Myfortic® 720 mg
BID
Study burden and risks
Occurence of extensive chronic GvHD has a high mortality.
This study investigates the value of addition of MPA to the reference treatment
CsA+PDN in the treatment of extensive chronic GvHD
This combination is possibly more effective en could thus lead to a shorter
treatmentperiod.
There are no extra procedures for this study, patientvisits and laboratory are
according to local practice.
There may be an increased risk on side effects with the addition of Myfortic
compared to the reference treatment.
EBMT-Trials Office - University College Hospital - 250 Euston Road
NW1 2PG London
United Kingdom
EBMT-Trials Office - University College Hospital - 250 Euston Road
NW1 2PG London
United Kingdom
Listed location countries
Age
Inclusion criteria
• Age 18 - 60
• Any primary diagnosis requiring treatment by hematopoietic stem cell transplantation (HSCT)
• Recipient of a single allogeneic stem cell transplant (bone marrow or peripheral blood stem cells, or cord blood) minimum 80 days ago
• Transplant from a related or unrelated donor
• Conditioning regimen: Myeloablative (MA) or non-myeloablative (NMA)
• Patients with a first episode of extensive chronic GvHD, without recurrent disease
• The diagnosis of chronic GvHD as defined by the NIH diagnostic and scoring system:
-With clear distinction from acute GvHD
-With presence of at least one diagnostic clinical sign of chronic GvHD or presence of at least 1 distinctive manifestation confirmed bypertinent biopsy or other relevant diagnostic tests
-Exclusion of other possible diagnoses
• Receiving a standard prophylaxis regimen for acute GvHD: CsA alone, CsA plus methotrexate or CsA+MMF for NMA, or a T-cell depleted transplantation (Patients may be started on CsA + steroids pre randomisation but may not be on treatment for more than 3 days pre randomisation)
• Negative pregnancy test in females of child-bearing potential - see section 5.4
• Patient gives written informed consent prior to randomisation
Exclusion criteria
• Age less than 18 or over 60 years old
• GvHD prophylaxis by tacrolimus plus methotroxate
• Delayed onset acute GvHD following NMA or DLI
• Second allogeneic stem cell transplant
• Not the first episode of chronic GvHD needing systemic immunosuppressive therapy
• Limited chronic GvHD (Seattle criteria)
• MMF used to prevent or treat GvHD in the previous 4 weeks
• Neutropenia (<1.0 x 109/l)
• Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient*s death
within 1 week of randomisation
• In the opinion of the investigator, if the patient has significant medical or psychosocial problems or unstable disease status
• Pregnant or lactating females, - see section 5.4
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2005-006178-86-NL |
| CCMO | NL15594.068.07 |