- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00929695
Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease
A Phase III Study to Determine Efficacy and Safety of Low-Dose Glucocorticoids for Initial Treatment of Acute Graft-versus-Host Disease
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (Low-dose)
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
immunosuppressive drug
Other Names:
immunosuppressive drug
Other Names:
|
Active Comparator: Arm II (Standard-dose)
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
immunosuppressive drug
Other Names:
immunosuppressive drug
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
Time Frame: At day 42 after initiation of treatment
|
The total cumulative dose of prednisone (milligrams/kilogram) was calculated starting from the start of therapy through study day 42.
|
At day 42 after initiation of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prednisone-associated Toxicity as Assessed by Hyperglycemia
Time Frame: Baseline and then through 42 days after starting treatment
|
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.
|
Baseline and then through 42 days after starting treatment
|
Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)
Time Frame: Baseline and through 100 days of treatment
|
The total number of invasive infections (bacterial, fungal and viral) occurring in patients in each group were collected.
|
Baseline and through 100 days of treatment
|
Prednisone-associated Toxicity as Assessed by Myopathy
Time Frame: Baseline and then weekly until 42 days after starting treatment
|
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.
|
Baseline and then weekly until 42 days after starting treatment
|
Prednisone-associated Toxicity as Assessed by Hypertension
Time Frame: Baseline and then through 42 days after starting treatment
|
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.
|
Baseline and then through 42 days after starting treatment
|
Prednisone-associated Toxicity as Assessed by Quality of Life
Time Frame: Baseline and then every other week until 42 days after starting treatment
|
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.
|
Baseline and then every other week until 42 days after starting treatment
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Non-relapse Mortality
Time Frame: At 12 months after the start of prednisone therapy
|
Non-relapse mortality (NRM) is defined as death due to any cause in the absence of documented relapse/progression.
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At 12 months after the start of prednisone therapy
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Recurrent or Progressive Malignancy
Time Frame: At 12 months after the start of prednisone therapy
|
Percentage of relapse estimated by cumulative incidence methods
|
At 12 months after the start of prednisone therapy
|
Progression to Grade III-IV Acute GVHD
Time Frame: At approximately 100 days after transplant
|
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.
|
At approximately 100 days after transplant
|
Secondary Therapy for Acute GVHD Beyond Prednisone
Time Frame: At approximately 100 days after transplant
|
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.
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At approximately 100 days after transplant
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Chronic Extensive GVHD
Time Frame: At 12 months after the start of prednisone therapy
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Percentage of patients with chronic extensive GVHD, estimated by cumulative incidence methods
|
At 12 months after the start of prednisone therapy
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Overall Survival
Time Frame: At 12 months after the start of prednisone therapy
|
Percentage of patients surviving as estimated by Kaplan-Meier.
|
At 12 months after the start of prednisone therapy
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, Lymphoid
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Graft vs Host Disease
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- Prednisone
Other Study ID Numbers
- 2327.00
- P01CA018029 (U.S. NIH Grant/Contract)
- NCI-2010-00323 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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