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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Graft vs Host Disease

Intervention / Treatment
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* Drug: Rituximab
* Drug: Prednisone
* Drug: Cyclosporine A
* Drug: tacrolimus


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rituximab + prednisone arm<br>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. | Drug: Rituximab<br>* 375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9<br>* Other names: Rituxan;Drug: Prednisone<br>* 1 mg/kg; po per day with taper<br>* Other names: Orasone;Drug: Cyclosporine A<br>* trough 200-300 or lower; po<br>* Other names: Ciclosporin;Drug: tacrolimus<br>* trough 5-10 or lower; po<br>* Other names: Fujimycin;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete and/or Partial GVHD Response | 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 | 6 months | 
| Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial | Participants that decreased total daily corticosteroids ≤ 0.25mg/kg one year after rituximab infusion began | 1 year | 
| Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation | Failure-free survival (FFS) was defined as participants who are surviving with no relapse and second line of cGVHD treatment. | 6 and 12 Months | 
| Overall Survival | Overall survival at 6 and 12 months | 6 and 12 months |