Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

PRIMARY OBJECTIVES:

I. 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.

• beclomethasone dipropionate (Drug), also known as BECLOMETH, Beclovent, Beconase, Qvar, Vancenase, Vanceril: Given orally
• placebo (Drug), also known as PLCB: Given orally
• tacrolimus (Drug), also known as Advagraf, FK 506, Prograf, Protopic: Given after transplant
• methotrexate (Drug), also known as Abitrexate, amethopterin, Folex, methylaminopterin, Mexate, MTX: Given after transplant
• allogeneic hematopoietic stem cell transplantation (Procedure): Undergo stem cell transplant

Primary outcomes

• 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 outcomes

• 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]

Sex: All

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

• Paul Martin, Principal investigator, Fred Hutchinson Cancer Center