Back to resultsLow-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease
Primary Purpose
Graft Versus Host Disease, Recurrent Adult Acute Lymphoblastic Leukemia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
prednisone
methylprednisolone
questionnaire administration
Sponsored by
About this trial
This is an interventional supportive care trial for Graft Versus Host Disease
Eligibility Criteria
Inclusion Criteria:
- Patients with newly diagnosed acute GVHD (>= grade IIa) for whom, in the judgment of the attending physician, initial treatment with systemic glucocorticoids is indicated
- Patient or guardian able and willing to provide informed consent
Exclusion Criteria:
- Hallmarks of chronic GVHD
- GVHD after donor lymphocyte infusion (DLI)
- Patient unwilling to remain in Seattle under the care of the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) through day 42 after the start of treatment for GVHD
- Uncontrolled infection or other underlying comorbidity (i.e. severe psychiatric illness) that precludes the use of "standard-dose" prednisone
- Recent diagnosis of recurrent or progressive malignancy that precludes the use of "standard-dose" prednisone
- Any prior systemic therapy for acute GVHD (Patients may receive up to 2 doses of low-dose prednisone prior to randomization; low-dose prednisone is defined as 0.5 mg/kg/dose for patients who present with grade IIa GVHD and 1 mg/kg/dose for those who present with grade IIb-IV GVHD)
- Enrollment on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) trial 0802
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm I (Low-dose)
Arm II (Standard-dose)
Arm Description
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
The total cumulative dose of prednisone (milligrams/kilogram) was calculated starting from the start of therapy through study day 42.
Secondary Outcome Measures
Prednisone-associated Toxicity as Assessed by Hyperglycemia
Impact on blood glucose (BG) control will be assessed by comparing average BG and BG-variability between patients given standard-dose and low-dose prednisone.
Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)
The total number of invasive infections (bacterial, fungal and viral) occurring in patients in each group were collected.
Prednisone-associated Toxicity as Assessed by Myopathy
Assessed by mean change from baseline to day 42 using Manual Muscle Testing measure. The degree of resistance against pressure applied by tester was measured on a 5-point scale. A score of 5 indicates the patient can hold the position against maximum to strong resistance. A score of 0 indicates the patient has no resistance against pressure. Testing included upper and lower extremities: shoulder (deltoid at 90 degrees), and hip and knee in a sitting position.
Prednisone-associated Toxicity as Assessed by Hypertension
The number of different anti-hypertensive medications administered to control hypertension were collected. The mean change in the number of medications from baseline to day 42 was measured.
Prednisone-associated Toxicity as Assessed by Quality of Life
Patients completed the MD Anderson Symptom Inventory (MDASI), which is a quality of life questionnaire validated for oncology/transplant patients. On a 1-10 point scale, patients scored the degree of severity of symptoms or the degree of interference in feelings or function due to symptoms at baseline or in the previous week. A score of 1 indicates symptom is not present or does not interfere with feelings or function. A score of 10 indicates the symptom is as bad as you can imagine or interferes completely with feelings or function. The mean change in score from baseline to day 42 was measured.
Non-relapse Mortality
Non-relapse mortality (NRM) is defined as death due to any cause in the absence of documented relapse/progression.
Recurrent or Progressive Malignancy
Percentage of relapse estimated by cumulative incidence methods
Progression to Grade III-IV Acute GVHD
Diagnosed and graded according to standard established criteria. Measure is percent of patients with baseline scores of IIa (Group A) or IIb (Group B) who progressed to more severe GVHD (Grade III/IV). Percentage estimated by cumulative incidence methods.
Secondary Therapy for Acute GVHD Beyond Prednisone
This includes any intervention intended to control acute GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not given previously. This does not include topical therapy, an increase in the dose of glucocorticoids or the resumption of treatment after previous discontinuation or any increase in the dose of immunosuppressive medication previously administered for GVHD prophylaxis, or reinstatement of GVHD prophylaxis previously discontinued. A change in treatment from cyclosporine to tacrolimus or vice versa because of drug toxicity is not considered secondary therapy, but any change made because of uncontrolled GVHD is considered secondary therapy. Percentage is estimated by cumulative incidence methods.
Chronic Extensive GVHD
Percentage of patients with chronic extensive GVHD, estimated by cumulative incidence methods
Overall Survival
Percentage of patients surviving as estimated by Kaplan-Meier.
Full Information
NCT ID
NCT00929695
First Posted
June 25, 2009
Last Updated
July 19, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00929695
Brief Title
Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease
Official Title
A Phase III Study to Determine Efficacy and Safety of Low-Dose Glucocorticoids for Initial Treatment of Acute Graft-versus-Host Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
December 14, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
This randomized phase III trial is studying low-dose prednisone or methylprednisolone to see how well they work compared with standard-dose prednisone or methylprednisolone in treating patients with newly diagnosed acute graft-versus-host disease (GVHD). Glucocorticoids, such as prednisone or methylprednisolone at a starting dose of 2 mg/kg/day are standard treatment for acute graft-versus-host disease caused by a donor stem cell transplant. It is not yet known whether low-dose glucocorticoids are more effective than standard-dose glucocorticoids in treating acute graft-versus-host-disease
Detailed Description
OBJECTIVES:
I. To determine whether a lower starting dose of prednisone for treatment of newly diagnosed acute GVHD results in decreased prednisone exposure without compromising overall survival.
II. To estimate the magnitude of clinical benefit associated with the reduction in prednisone exposure.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (Low-dose; prednisone-equivalent dose at initiation of treatment of 0.5 mg/kg/day or 1.0 mg/kg/day; stratified according to initial symptom severity): Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
ARM II (Standard-dose; prednisone-equivalent dose at initiation of treatment of 1.0 mg/kg/day or 2.0 mg/kg/day; stratified according to initial symptom severity): Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 year and then annually thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Recurrent Adult Acute Lymphoblastic Leukemia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (Low-dose)
Arm Type
Experimental
Arm Description
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (Standard-dose)
Arm Type
Active Comparator
Arm Description
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
immunosuppressive drug
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Other Intervention Name(s)
Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort
Intervention Description
immunosuppressive drug
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
Description
The total cumulative dose of prednisone (milligrams/kilogram) was calculated starting from the start of therapy through study day 42.
Time Frame
At day 42 after initiation of treatment
Secondary Outcome Measure Information:
Title
Prednisone-associated Toxicity as Assessed by Hyperglycemia
Description
Impact on blood glucose (BG) control will be assessed by comparing average BG and BG-variability between patients given standard-dose and low-dose prednisone.
Time Frame
Baseline and then through 42 days after starting treatment
Title
Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)
Description
The total number of invasive infections (bacterial, fungal and viral) occurring in patients in each group were collected.
Time Frame
Baseline and through 100 days of treatment
Title
Prednisone-associated Toxicity as Assessed by Myopathy
Description
Assessed by mean change from baseline to day 42 using Manual Muscle Testing measure. The degree of resistance against pressure applied by tester was measured on a 5-point scale. A score of 5 indicates the patient can hold the position against maximum to strong resistance. A score of 0 indicates the patient has no resistance against pressure. Testing included upper and lower extremities: shoulder (deltoid at 90 degrees), and hip and knee in a sitting position.
Time Frame
Baseline and then weekly until 42 days after starting treatment
Title
Prednisone-associated Toxicity as Assessed by Hypertension
Description
The number of different anti-hypertensive medications administered to control hypertension were collected. The mean change in the number of medications from baseline to day 42 was measured.
Time Frame
Baseline and then through 42 days after starting treatment
Title
Prednisone-associated Toxicity as Assessed by Quality of Life
Description
Patients completed the MD Anderson Symptom Inventory (MDASI), which is a quality of life questionnaire validated for oncology/transplant patients. On a 1-10 point scale, patients scored the degree of severity of symptoms or the degree of interference in feelings or function due to symptoms at baseline or in the previous week. A score of 1 indicates symptom is not present or does not interfere with feelings or function. A score of 10 indicates the symptom is as bad as you can imagine or interferes completely with feelings or function. The mean change in score from baseline to day 42 was measured.
Time Frame
Baseline and then every other week until 42 days after starting treatment
Title
Non-relapse Mortality
Description
Non-relapse mortality (NRM) is defined as death due to any cause in the absence of documented relapse/progression.
Time Frame
At 12 months after the start of prednisone therapy
Title
Recurrent or Progressive Malignancy
Description
Percentage of relapse estimated by cumulative incidence methods
Time Frame
At 12 months after the start of prednisone therapy
Title
Progression to Grade III-IV Acute GVHD
Description
Diagnosed and graded according to standard established criteria. Measure is percent of patients with baseline scores of IIa (Group A) or IIb (Group B) who progressed to more severe GVHD (Grade III/IV). Percentage estimated by cumulative incidence methods.
Time Frame
At approximately 100 days after transplant
Title
Secondary Therapy for Acute GVHD Beyond Prednisone
Description
This includes any intervention intended to control acute GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not given previously. This does not include topical therapy, an increase in the dose of glucocorticoids or the resumption of treatment after previous discontinuation or any increase in the dose of immunosuppressive medication previously administered for GVHD prophylaxis, or reinstatement of GVHD prophylaxis previously discontinued. A change in treatment from cyclosporine to tacrolimus or vice versa because of drug toxicity is not considered secondary therapy, but any change made because of uncontrolled GVHD is considered secondary therapy. Percentage is estimated by cumulative incidence methods.
Time Frame
At approximately 100 days after transplant
Title
Chronic Extensive GVHD
Description
Percentage of patients with chronic extensive GVHD, estimated by cumulative incidence methods
Time Frame
At 12 months after the start of prednisone therapy
Title
Overall Survival
Description
Percentage of patients surviving as estimated by Kaplan-Meier.
Time Frame
At 12 months after the start of prednisone therapy
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with newly diagnosed acute GVHD (>= grade IIa) for whom, in the judgment of the attending physician, initial treatment with systemic glucocorticoids is indicated
Patient or guardian able and willing to provide informed consent
Exclusion Criteria:
Hallmarks of chronic GVHD
GVHD after donor lymphocyte infusion (DLI)
Patient unwilling to remain in Seattle under the care of the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) through day 42 after the start of treatment for GVHD
Uncontrolled infection or other underlying comorbidity (i.e. severe psychiatric illness) that precludes the use of "standard-dose" prednisone
Recent diagnosis of recurrent or progressive malignancy that precludes the use of "standard-dose" prednisone
Any prior systemic therapy for acute GVHD (Patients may receive up to 2 doses of low-dose prednisone prior to randomization; low-dose prednisone is defined as 0.5 mg/kg/dose for patients who present with grade IIa GVHD and 1 mg/kg/dose for those who present with grade IIb-IV GVHD)
Enrollment on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) trial 0802
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco Mielcarek
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease
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