Trial Outcomes & Findings for A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease (NCT NCT00350545)
NCT ID: NCT00350545
Last Updated: 2017-11-20
Results Overview
Participants that have successfully tapered prednisone to a dose of 0.25 mg/kg/Day by 6 Months without clinical relapse.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
37 participants
Primary outcome timeframe
6 months
Results posted on
2017-11-20
Participant Flow
Participant milestones
| Measure |
Rituximab + Prednisone Arm
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
35
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Rituximab + Prednisone Arm
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease
Baseline characteristics by cohort
| Measure |
Rituximab + Prednisone Arm
n=37 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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
Participants that have successfully tapered prednisone to a dose of 0.25 mg/kg/Day by 6 Months without clinical relapse.
Outcome measures
| Measure |
Rituximab + Prednisone Arm
n=35 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Number of Participants With the Ability to Successfully Taper Prednisone to a Dose Lower Dose.
|
14 Participants
|
SECONDARY outcome
Timeframe: 6 monthsTo 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
Outcome measures
| Measure |
Rituximab + Prednisone Arm
n=35 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Number of Participants With Complete and/or Partial GVHD Response
Complete response
|
12 Participants
|
|
Number of Participants With Complete and/or Partial GVHD Response
Partial response
|
15 Participants
|
SECONDARY outcome
Timeframe: 1 yearParticipants that decreased total daily corticosteroids ≤ 0.25mg/kg one year after rituximab infusion began
Outcome measures
| Measure |
Rituximab + Prednisone Arm
n=35 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial
|
14 Participants
|
SECONDARY outcome
Timeframe: 6 and 12 MonthsPopulation: 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.
Failure-free survival (FFS) was defined as participants who are surviving with no relapse and second line of cGVHD treatment.
Outcome measures
| Measure |
Rituximab + Prednisone Arm
n=35 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation
6 month FFS
|
28 Participants
|
|
Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation
12 month FFS
|
21 Participants
|
SECONDARY outcome
Timeframe: 6 and 12 monthsOverall survival at 6 and 12 months
Outcome measures
| Measure |
Rituximab + Prednisone Arm
n=35 Participants
To determine the efficacy of Rituximab as first line of treatment of chronic GVHD.
|
|---|---|
|
Overall Survival
6 month overall survival
|
33 Participants
|
|
Overall Survival
12 month overall survival
|
30 Participants
|
Adverse Events
Rituximab + Prednisone Arm
Serious events: 35 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab + Prednisone Arm
n=35 participants at risk
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: 375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9
Prednisone: 1 mg/kg; po per day with taper
Cyclosporine A: trough 200-300 or lower; po
tacrolimus: trough 5-10 or lower; po
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
17.1%
6/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Nocardia infection
|
2.9%
1/35 • 4 years
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
8.6%
3/35 • 4 years
|
|
Blood and lymphatic system disorders
Abscess
|
8.6%
3/35 • 4 years
|
|
Blood and lymphatic system disorders
Low absolute neutrophil count
|
2.9%
1/35 • 4 years
|
|
Infections and infestations
Bacterial infection
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
bilirubin levels increasing
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
Blood
|
5.7%
2/35 • 4 years
|
|
Cardiac disorders
Cardiac arrest
|
2.9%
1/35 • 4 years
|
|
Cardiac disorders
Chest pain
|
5.7%
2/35 • 4 years
|
|
General disorders
Graft versus host disease
|
34.3%
12/35 • 4 years
|
|
General disorders
Confusion
|
2.9%
1/35 • 4 years
|
|
Eye disorders
Conjunctivitis
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.6%
3/35 • 4 years
|
|
General disorders
Death
|
14.3%
5/35 • 4 years
|
|
Renal and urinary disorders
Diarrhea
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/35 • 4 years
|
|
Skin and subcutaneous tissue disorders
Erythematous rash
|
2.9%
1/35 • 4 years
|
|
General disorders
Fever
|
5.7%
2/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
H1N1
|
2.9%
1/35 • 4 years
|
|
Cardiac disorders
Tachycardia
|
5.7%
2/35 • 4 years
|
|
Renal and urinary disorders
Veno-occlusive disease
|
2.9%
1/35 • 4 years
|
|
Musculoskeletal and connective tissue disorders
Osteomyelitis
|
2.9%
1/35 • 4 years
|
|
Renal and urinary disorders
Tbili
|
5.7%
2/35 • 4 years
|
|
Blood and lymphatic system disorders
Syncope
|
5.7%
2/35 • 4 years
|
|
General disorders
Stroke
|
5.7%
2/35 • 4 years
|
|
Infections and infestations
Sespis
|
5.7%
2/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory syncytial virus
|
5.7%
2/35 • 4 years
|
|
General disorders
Multi-organ system failure
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
Ischemia
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Disseminated aspergillus
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.6%
3/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Sinus bradycardia
|
2.9%
1/35 • 4 years
|
Other adverse events
| Measure |
Rituximab + Prednisone Arm
n=35 participants at risk
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: 375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9
Prednisone: 1 mg/kg; po per day with taper
Cyclosporine A: trough 200-300 or lower; po
tacrolimus: trough 5-10 or lower; po
|
|---|---|
|
General disorders
Fever
|
8.6%
3/35 • 4 years
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
2.9%
1/35 • 4 years
|
|
General disorders
Cold symptoms
|
2.9%
1/35 • 4 years
|
|
Gastrointestinal disorders
Constipation
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Decrease in diffusing capacity of the lungs for carbon monoxide
|
2.9%
1/35 • 4 years
|
|
Gastrointestinal disorders
Diarrhea
|
5.7%
2/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.7%
2/35 • 4 years
|
|
Gastrointestinal disorders
Pain
|
8.6%
3/35 • 4 years
|
|
Infections and infestations
Infections
|
5.7%
2/35 • 4 years
|
|
Skin and subcutaneous tissue disorders
Erythematous
|
5.7%
2/35 • 4 years
|
|
Blood and lymphatic system disorders
Hypertensive
|
2.9%
1/35 • 4 years
|
|
Immune system disorders
influenza A
|
2.9%
1/35 • 4 years
|
|
Gastrointestinal disorders
Nausea
|
2.9%
1/35 • 4 years
|
|
Blood and lymphatic system disorders
Orthostatic hypotension
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus disease
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
slight decrease in her forced expiratory volume in 1 second
|
2.9%
1/35 • 4 years
|
|
Renal and urinary disorders
Urinary tract infection
|
2.9%
1/35 • 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
2.9%
1/35 • 4 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place