None listed
Conditions
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.
Interventions
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 indu
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.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed