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):
Marco Mielcarek, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00929695
First received: June 25, 2009
Last updated: October 8, 2014
Last verified: October 2014
  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:
  • Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment [ Time Frame: At day 42 after initiation of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and then through 42 days after starting treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and through 100 days of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and then weekly until 42 days after starting treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and then through 42 days after starting treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and then every other week until 42 days after starting treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 12 months after the start of prednisone therapy ] [ Designated as safety issue: Yes ]
    Non-relapse mortality (NRM) is defined as death due to any cause in the absence of documented relapse/progression.

  • Recurrent or Progressive Malignancy [ Time Frame: At 12 months after the start of prednisone therapy ] [ Designated as safety issue: Yes ]
    Percentage of relapse estimated by cumulative incidence methods

  • Progression to Grade III-IV Acute GVHD [ Time Frame: At approximately 100 days after transplant ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At approximately 100 days after transplant ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 12 months after the start of prednisone therapy ] [ Designated as safety issue: Yes ]
    Percentage of patients with chronic extensive GVHD, estimated by cumulative incidence methods

  • Overall Survival [ Time Frame: At 12 months after the start of prednisone therapy ] [ Designated as safety issue: Yes ]
    Percentage of patients surviving as estimated by Kaplan-Meier.


Enrollment: 164
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: Marco Mielcarek, Principal Investigator, 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
Results First Received: September 19, 2014
Last Updated: October 8, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Prednisone
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 23, 2014