Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Beclomethasone dipropionate may be effective in preventing acute graft-versus-host disease in patients undergoing a stem cell transplant for hematologic cancer.
PURPOSE: This randomized phase II trial is studying how well beclomethasone dipropionate works in preventing acute graft-versus-host disease in patients undergoing a donor stem cell transplant for hematologic cancer.
Detailed Description
PRIMARY OBJECTIVES:
- Assess the efficacy of oral BDP for prevention of acute GVHD after allogeneic hematopoietic cell transplantation with myeloablative conditioning regimens.
OUTLINE:
Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral beclomethasone dipropionate 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplant. Patients also receive a standard immunosuppressive regimen comprising tacrolimus and methotrexate post-transplant.
ARM II: Patients receive oral placebo 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplant. Patients also receive a standard immunosuppressive regimen comprising tacrolimus and methotrexate post-transplant.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I Patients receive oral beclomethasone dipropionate 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplant. Patients also receive a standard immunosuppressive regimen comprising tacrolimus and methotrexate post-transplant. |
Drug: beclomethasone dipropionate
Given orally
Other Names:
Drug: tacrolimus
Given after transplant
Other Names:
Drug: methotrexate
Given after transplant
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo stem cell transplant
|
| Active Comparator: Arm II Patients receive oral placebo 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplant. Patients also receive a standard immunosuppressive regimen comprising tacrolimus and methotrexate post-transplant. |
Drug: placebo
Given orally
Other Names:
Drug: tacrolimus
Given after transplant
Other Names:
Drug: methotrexate
Given after transplant
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo stem cell transplant
|
Outcome Measures
Primary Outcome Measures
- Development of acute graft-versus-host disease (GVHD) with severity sufficient to require systemic immunosuppressive treatment [On or before day 90 after the transplant]
Secondary Outcome Measures
- Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight [First 75 days after HCT]
- Peak and average skin, liver and gut morbidity stages and overall grades [To day 90 after HCT]
- Modified average acute GVHD index score [To day 90 after HCT]
- Cumulative incidence of systemic immunosuppressive treatment for acute GVHD [At any time after HCT]
- Cumulative incidence of topical therapy for acute GVHD, including psoralen and UV irradiation, hydrocortisone cream, topical tacrolimus, oral BDP, or oral swish and spit dexamethasone [On or before day 90 after the transplant]
- Cumulative incidence of biopsy-proven gastrointestinal GVHD [On or before day 90 after the transplant]
- Proportion of patients with grade IIa GVHD [On or before day 90 after the transplant]
- Proportions of patients with grades IIa and IIb - IV GVHD [On or before day 90 after the transplant]
- Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment [At any time after HCT]
- Number of days in the hospital [During the first 90 days after HCT]
- Non-relapse mortality [At any time after HCT]
- Overall survival [At any time after HCT]
- Survival [At 200 days after HCT]
- Safety [On or before day 90 after the transplant]
- Feasibility [First 75 days after HCT]
- Survival without recurrent malignancy [At any time after HCT]
Eligibility Criteria
Criteria
Inclusion
-
Allogeneic HCT with marrow or growth-factor mobilized blood cells from an HLA-A, B, C, DRB1, and HLA-DQB1-allele matched or single-allele or antigen mismatched related or unrelated donor
-
Use of myeloablative pre-transplant conditioning regimen with > 800 cGy total body irradiation and cyclophosphamide, or high-dose busulfan and cyclophosphamide
-
Use of methotrexate and tacrolimus for prevention of GVHD after allogeneic HCT
-
Informed consent document signed
Exclusion
-
Cord blood transplant recipients
-
Use of T cell depletion or rabbit antithymocyte globulin to prevent acute GVHD
-
Treatment with rabbit antithymocyte globulin or alemtuzumab within 3 months before the date of HCT
-
Participation in another therapeutic trial where the primary endpoint is related to acute GVHD
-
Hospitalization at the beginning of the pre-transplant conditioning regimen because of pre-existing medical complications
-
Glucocorticoid treatment at prednisone-equivalent doses > 0.2 mg/kg/day
-
Known intolerance to BDP
-
Anticipated inability to tolerate oral administration of study drug tablets for any reason during the first two weeks after HCT
-
Body weight < 35 kg (lower-dose formulations are not available for subjects with lower body weight)
-
Pregnancy or breast feeding
-
Women of child-bearing potential who are unwilling to use a reliable method of contraception
-
Incarceration
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 2 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
Investigators
- Principal Investigator: Paul Martin, Fred Hutchinson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2079.00
- NCI-2009-01544