Graft Versus Host DiseasePhase 3NCT00929695
Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease
A Phase 3 study testing prednisone, methylprednisolone and questionnaire administration in people with Graft Versus Host Disease and Recurrent Adult Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Graft Versus Host Disease, Recurrent Adult Acute Lymphoblastic Leukemia
- What is being tested?
- prednisone, methylprednisolone and questionnaire administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to 14 Dec 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: 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
Read the detailed description
OBJECTIVES:
- 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.
- Being tested
- prednisone, methylprednisolone, questionnaire administration
- Medical subject headings
- Graft vs Host Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisoneDrug
Also called DeCortin, Deltra
immunosuppressive drug
Also called Depo-Medrol, Medrol, MePRDL, Solu-Medrol
immunosuppressive drug
questionnaire administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Low-dose) | Experimental | Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity. Receives: Drug: prednisone; Drug: methylprednisolone; Other: questionnaire administration |
| Arm II (Standard-dose) | Active comparator | Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity. Receives: Drug: prednisone; Drug: methylprednisolone; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
The total cumulative dose of prednisone (milligrams/kilogram) was calculated starting from the start of therapy through study day 42.
Measured: At day 42 after initiation of treatment
Secondary outcomes (11)
Prednisone-associated Toxicity as Assessed by Hyperglycemia
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.
Measured: Baseline and then through 42 days after starting treatment
Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)
The total number of invasive infections (bacterial, fungal and viral) occurring in patients in each group were collected.
Measured: Baseline and through 100 days of treatment
Prednisone-associated Toxicity as Assessed by Myopathy
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.
Measured: Baseline and then weekly until 42 days after starting treatment
Prednisone-associated Toxicity as Assessed by Hypertension
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.
Measured: Baseline and then through 42 days after starting treatment
Prednisone-associated Toxicity as Assessed by Quality of Life
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.
Measured: Baseline and then every other week until 42 days after starting treatment
Non-relapse Mortality
Non-relapse mortality (NRM) is defined as death due to any cause in the absence of documented relapse/progression.
Measured: At 12 months after the start of prednisone therapy
Recurrent or Progressive Malignancy
Percentage of relapse estimated by cumulative incidence methods
Measured: At 12 months after the start of prednisone therapy
Progression to Grade III-IV Acute GVHD
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.
Measured: At approximately 100 days after transplant
Secondary Therapy for Acute GVHD Beyond Prednisone
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.
Measured: At approximately 100 days after transplant
Chronic Extensive GVHD
Percentage of patients with chronic extensive GVHD, estimated by cumulative incidence methods
Measured: At 12 months after the start of prednisone therapy
Overall Survival
Percentage of patients surviving as estimated by Kaplan-Meier.
Measured: At 12 months after the start of prednisone therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionJul 2013
- Study completion14 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Marco Mielcarek, Fred Hutchinson Cancer Center
- Investigators
- Marco Mielcarek, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929695
- Sponsor's protocol ID
- 2327.00
- Other IDs
- NCI-2010-00323, P01CA018029
- Status last verified
- Jul 2017
- First submitted
- 25 Jun 2009
- Last updated
- 21 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study to Determine Efficacy and Safety of Low-Dose Glucocorticoids for Initial Treatment of Acute Graft-versus-Host Disease
- ClinicalTrials.gov ID
- NCT00929695
- Acronym / sponsor ID
- 2327.00
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- 14 Dec 2015 (actual)
- First posted
- 29 Jun 2009 (estimated)
- Results
- Posted 9 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (Low-dose) | Experimental | Drug: prednisone, Drug: methylprednisolone, Other: questionnaire administrationPatients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity. |
| Arm II (Standard-dose) | Active comparator | Drug: prednisone, Drug: methylprednisolone, Other: questionnaire administrationPatients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| prednisoneAlso: DeCortin, Deltraimmunosuppressive drug | Drug | Arm I (Low-dose), Arm II (Standard-dose) |
| methylprednisoloneAlso: Depo-Medrol, Medrol, MePRDL, Solu-Medrolimmunosuppressive drug | Drug | Arm I (Low-dose), Arm II (Standard-dose) |
| questionnaire administrationAncillary studies | Other | Arm I (Low-dose), Arm II (Standard-dose) |
Primary outcome
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.
11 secondary outcomes
Prednisone-associated Toxicity as Assessed by Hyperglycemia
Time frame: 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
Prednisone-associated Toxicity as Assessed by Myopathy
Time frame: 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
Prednisone-associated Toxicity as Assessed by Quality of Life
Time frame: Baseline and then every other week until 42 days after starting treatment
Non-relapse Mortality
Time frame: At 12 months after the start of prednisone therapy
Recurrent or Progressive Malignancy
Time frame: At 12 months after the start of prednisone therapy
Progression to Grade III-IV Acute GVHD
Time frame: At approximately 100 days after transplant
Secondary Therapy for Acute GVHD Beyond Prednisone
Time frame: At approximately 100 days after transplant
Chronic Extensive GVHD
Time frame: At 12 months after the start of prednisone therapy
Overall Survival
Time frame: At 12 months after the start of prednisone therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Mielcarek principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing prednisone, methylprednisolone and questionnaire administration in people with Graft Versus Host Disease and Recurrent Adult Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment (time frame: At day 42 after initiation of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2017.