Graft vs Host Disease
Conditions
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.
Interventions
DRUGRituximab
375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9
DRUGPrednisone
1 mg/kg; po per day with taper
DRUGCyclosporine A
trough 200-300 or lower; po
DRUGtacrolimus
trough 5-10 or lower; po
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + Prednisone Arm To determine the efficacy of Rituximab as first line of treatment of chronic GVHD. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Rituximab + Prednisone Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 35 |
| serious Total, serious adverse events | 35 / 35 |
Outcome results
Primary
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.
Time frame: 6 months
Population: Participants who have complete or partial clinical response to therapy as well as a steroid dose, tapered to \<0.25 mg/kg/day within 6 months after initiation of rituximab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab + Prednisone Arm | Number of Participants With the Ability to Successfully Taper Prednisone to a Dose Lower Dose. | 14 Participants |
Secondary
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.
Time frame: 6 and 12 Months
Population: At initiation of therapy, all patients were on high dose of steroids (1mg/kg/day). Failure-free survival (FFS) rate for the 31 patients at 6 and 12 months post-rituximab initiation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab + Prednisone Arm | Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation | 6 month FFS | 28 Participants |
| Rituximab + Prednisone Arm | Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation | 12 month FFS | 21 Participants |
Secondary
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
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab + Prednisone Arm | Number of Participants With Complete and/or Partial GVHD Response | Complete response | 12 Participants |
| Rituximab + Prednisone Arm | Number of Participants With Complete and/or Partial GVHD Response | Partial response | 15 Participants |
Secondary
Overall Survival
Overall survival at 6 and 12 months
Time frame: 6 and 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab + Prednisone Arm | Overall Survival | 6 month overall survival | 33 Participants |
| Rituximab + Prednisone Arm | Overall Survival | 12 month overall survival | 30 Participants |
Secondary
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
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab + Prednisone Arm | Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial | 14 Participants |