Clinical trial NCT00929695: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft Versus Host Disease
Recurrent Adult Acute Lymphoblastic Leukemia
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-06-29
Enrollment: 164
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
timeFrame: At day 42 after initiation of treatment
Secondary outcomes:
measure: Prednisone-associated Toxicity as Assessed by Hyperglycemia
timeFrame: Baseline and then through 42 days after starting treatment
measure: Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)
timeFrame: Baseline and through 100 days of treatment
measure: Prednisone-associated Toxicity as Assessed by Myopathy
timeFrame: Baseline and then weekly until 42 days after starting treatment
measure: Prednisone-associated Toxicity as Assessed by Hypertension
timeFrame: Baseline and then through 42 days after starting treatment
measure: Prednisone-associated Toxicity as Assessed by Quality of Life
timeFrame: Baseline and then every other week until 42 days after starting treatment
measure: Non-relapse Mortality
timeFrame: At 12 months after the start of prednisone therapy
measure: Recurrent or Progressive Malignancy
timeFrame: At 12 months after the start of prednisone therapy
measure: Progression to Grade III-IV Acute GVHD
timeFrame: At approximately 100 days after transplant
measure: Secondary Therapy for Acute GVHD Beyond Prednisone
timeFrame: At approximately 100 days after transplant
measure: Chronic Extensive GVHD
timeFrame: At 12 months after the start of prednisone therapy
measure: Overall Survival
timeFrame: At 12 months after the start of prednisone therapy
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Marco Mielcarek
role: PRINCIPAL_INVESTIGATOR
References: