A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease

Not Applicable

Completed

Conditions: Graft vs Host Disease

Interventions: Drug: Rituximab
Drug: Prednisone
Drug: Cyclosporine A
Drug: tacrolimus

Registration Number: NCT00350545

Lead Sponsor: Stanford University

Brief Summary: The addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, enable a more rapid and effective steroid taper.

Detailed Description: To determine the efficacy of Rituximab as first line of treatment of chronic GVHD. Efficacy will be defined as he ability to taper prednisone to a dose of 0.25 mg/kg per day by 6 months without clinical or GVHD relapse/ recurrence.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Children and adults with a new diagnosis of chronic GVHD- that requires systemic immunosuppressive treatment to a dose of 1mg/kg/day prednisone and who have undergone any type of donor hematopoietic cell graft or conditioning regimen.
Stable doses of other immunosuppressive medications (e.g. calcineurin inhibitors, mycophenolate mofetil) for 2 weeks prior to enrollment. In addition, these other immunosuppressive medications should not be dose increased.
Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
All subjects must provide written informed consent.

Exclusion Criteria

Known life-threatening hypersensitivity to Rituximab or other anti-B cell antibody.
Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment. Persistent prednisone treatment of acute GVHD that is less than 1mg/kg is allowed.
Active, uncontrolled infection- CMV reactivation is excluded (i.e. pneumonitis, colitis). Peripheral blood CMV reactivation is allowed as long as it is not associated with CMV disease and is responding to therapy.
Known Hepatitis B surface Ag positive
Active malignant disease relapse.
Pregnancy
Lactating
Inability to comply with the Rituximab treatment regimen.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rituximab + prednisone arm	Cyclosporine A	Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.
rituximab + prednisone arm	Rituximab	Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.
rituximab + prednisone arm	Prednisone	Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.
rituximab + prednisone arm	tacrolimus	Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.

Primary Outcome Measures

Name	Time	Method
Number of Participants With the Ability to Successfully Taper Prednisone to a Dose Lower Dose.	6 months	Participants that have successfully tapered prednisone to a dose of 0.25 mg/kg/Day by 6 Months without clinical relapse.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Complete and/or Partial GVHD Response	6 months	To have physician documentation of clinical GVHD response using organ staging and scoring scale- NIH clinical GVHD consensus response criteria applied 6 months after rituximab infusion began
Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial	1 year	Participants that decreased total daily corticosteroids ≤ 0.25mg/kg one year after rituximab infusion began
Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation	6 and 12 Months	Failure-free survival (FFS) was defined as participants who are surviving with no relapse and second line of cGVHD treatment.
Overall Survival	6 and 12 months	Overall survival at 6 and 12 months