Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00929695
First received: June 25, 2009
Last updated: October 31, 2013
Last verified: October 2013

June 25, 2009
October 31, 2013
June 2009
July 2013   (final data collection date for primary outcome measure)
>= 33% reduction of cumulative prednisone dose with lower-dose prednisone compared to those given standard-dose prednisone [ Time Frame: At day 42 after initiation of treatment ] [ Designated as safety issue: No ]
Demonstrated in a prospective fashion.
At least 33% reduction of cumulative prednisone dose at day 42 in patients receiving lower-dose prednisone compared to those receiving standard-dose prednisone [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00929695 on ClinicalTrials.gov Archive Site
  • Prednisone-associated toxicity as assessed by hyperglycemia [ Time Frame: Baseline and through 6 weeks after enrollment ] [ Designated as safety issue: Yes ]
    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. BG levels will be retrieved from the FHCRC clinical database at the conclusion of study.
  • Prednisone-associated toxicity as assessed by invasive bacterial, viral, and fungal tissue or organ infections [ Time Frame: Baseline through 6 weeks ] [ Designated as safety issue: Yes ]
    Assessed in a prospective fashion. Other infection data will be retrieved from FHCRC and Infectious Disease databases at the conclusion of the study.
  • Prednisone-associated toxicity as assessed by myopathy [ Time Frame: Baseline and weekly for 6 weeks ] [ Designated as safety issue: Yes ]
    Assessed using four simple tests of muscle strength: i) 'Manual Muscle Testing" 5-Point Scale of upper and lower extremities; ii) 'Timed Stands Test' (measures lower extremity strength); iii) 'Timed Up and Go' test (measures mobility, balance and overall locomotor performance); and iv) 'Unilateral Forefoot Balance Test" (evaluates gluteus medius weakness).
  • Prednisone-associated toxicity as assessed by hypertension [ Time Frame: Baseline and weekly for 6 weeks ] [ Designated as safety issue: Yes ]
    The number of different anti-hypertensive medications will be abstracted from pharmacy records, the patient chart or the electronic record. Dose increments of individual medications will not be scored as a new medication.
  • Prednisone-associated toxicity as assessed by quality of life [ Time Frame: Baseline and every other week until 6 weeks ] [ Designated as safety issue: Yes ]
    Patients complete the MD Anderson Symptom Inventory (MDASI), which is a quality of life questionnaire validated for oncology/transplant patients.
  • Non-relapse and overall mortality defined as death due to any cause in the absence of documented relapse/progression [ Time Frame: At day 100 and 1 year ] [ Designated as safety issue: No ]
    We will regard a 7.5% excess in overall mortality as the allowable threshold for no-harm.
  • Recurrent or progressive malignancy [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Collected as part of long-term follow-up. Documented in a spreadsheet/case report form (CRF) and entered into an electronic database. The completed spreadsheet/CRF will be reviewed and signed by the PI.
  • Progression to grade III-IV acute GVHD [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Diagnosed and graded according to established criteria.
  • Secondary therapy for acute GVHD including any intervention intended to control GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not given previously [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Secondary systemic treatment is not indicated as long as there is continuing improvement in at least one manifestation of GVHD and no progression of any other manifestations. Initiated within 3-7 days whenever clinical manifestations of GVHD show evidence of progression in a previously involved organ or whenever clinical manifestations appear in an organ that was not previously involved. Secondary systemic treatment should be initiated within 10-14 days whenever manifestations of acute GVHD show no improvement during treatment with the originally prescribed medications.
  • Chronic extensive GVHD [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Collected as part of long-term follow-up.
  • Prednisone-related morbidity (e.g., hyperglycemia, infection, myopathy, hypertension, and quality of life) according to initial prednisone dose [ Designated as safety issue: Yes ]
  • Non-relapse and overall mortality at 1 year [ Designated as safety issue: No ]
  • Recurrent or progressive malignancy [ Designated as safety issue: No ]
  • Progression to grade III-IV acute graft-vs-host disease (GVHD) at 1 year [ Designated as safety issue: No ]
  • Secondary systemic therapy for acute GVHD at 1 year [ Designated as safety issue: No ]
  • Chronic extensive GVHD [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
  • Graft Versus Host Disease
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Drug: prednisone
    immunosuppressive drug
    Other Names:
    • DeCortin
    • Deltra
  • Drug: methylprednisolone
    immunosuppressive drug
    Other Names:
    • Depo-Medrol
    • Medrol
    • MePRDL
    • Solu-Medrol
    • Wyacort
  • Other: questionnaire administration
    Ancillary studies
  • 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.
    Interventions:
    • Drug: prednisone
    • Drug: methylprednisolone
    • Other: questionnaire administration
  • 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.
    Interventions:
    • Drug: prednisone
    • Drug: methylprednisolone
    • Other: questionnaire administration
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
150
Not Provided
July 2013   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00929695
2327.00, NCI-2010-00323, P01CA018029
Not Provided
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Marco Mielcarek Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP