ANTI-CD20 THERAPY FOR THE TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE

Rationale: Currently, there is no established therapy for steroid-refractory chronic GVHD. Manipulation of T cells has not been effective, while there is evidence that manipulation of the B cell compartment leads to clinical improvement.

Objective: To study prospectively the clinical efficacy of Rituximab treatment of steroid refractory chronic GVHD

Study design: Non-randomized phase II single center study

Study population: Patients with a steroid refractory chronic GVHD with skin localization
Intervention: Rituximab at a weekly dose of 375 mg/m2 i.v. for four weeks.

Main study parameters/endpoints The primary endpoint of the study will be the proportion of complete and partial responses. The secondary endpoint consists of immune-histochemical improvement in skin biopsies.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness. The burden and risks associated with this trial is very low. Potential benefit is that in vivo depletion of B cells with the CD20-specific antibody rituximab may result in amelioration of chronic GVHD symptoms. Side effects of rituximab are mostly associated with the first infusion and usually mild. Blood samples (50 ml each) will be collected at 8 different time points. Skin biopsies will be obtained at 3 different time points.

Anti CD20 therapy will result in complete or partial response in patients with chronic GVHD, who do not respond to first line treatment.

T=0 pre-treatment

Monthly until T=13 (1 year follow up)

Treatment with rituximab (anti-CD20 monoclonal antibody) 375 mg/m2 i.v. for four weeks (weekly)

Monthly clinical report and physical examination

3 x skin biopsy

3 x Shirmer test

7 x 40ml blood drawn