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
  Purpose

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


Condition Intervention Phase
Graft Versus Host Disease
Recurrent Adult Acute Lymphoblastic Leukemia
Drug: prednisone
Drug: methylprednisolone
Other: questionnaire administration
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase III Study to Determine Efficacy and Safety of Low-Dose Glucocorticoids for Initial Treatment of Acute Graft-versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • >= 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 150
Study Start Date: June 2009
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00929695

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Marco Mielcarek Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00929695     History of Changes
Other Study ID Numbers: 2327.00, NCI-2010-00323, P01CA018029
Study First Received: June 25, 2009
Last Updated: October 31, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids

ClinicalTrials.gov processed this record on July 20, 2014