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

Fred Hutchinson Cancer Center140 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Enrollment

140

Conditions

Hematopoietic/Lymphoid Cancer

Interventions

beclomethasone dipropionateDRUG

Given orally

placeboDRUG

Given orally

tacrolimusDRUG

Given after transplant

methotrexateDRUG

Given after transplant

allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo stem cell transplant

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Development of acute graft-versus-host disease (GVHD) with severity sufficient to require systemic immunosuppressive treatment

Time frame: On or before day 90 after the transplant

Secondary Outcomes

Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight

Time frame: First 75 days after HCT

Peak and average skin, liver and gut morbidity stages and overall grades

Time frame: To day 90 after HCT

Modified average acute GVHD index score

Time frame: To day 90 after HCT

Cumulative incidence of systemic immunosuppressive treatment for acute GVHD

Time frame: 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

Time frame: On or before day 90 after the transplant

Cumulative incidence of biopsy-proven gastrointestinal GVHD

Time frame: On or before day 90 after the transplant

Proportion of patients with grade IIa GVHD

Time frame: On or before day 90 after the transplant

Proportions of patients with grades IIa and IIb - IV GVHD

Time frame: On or before day 90 after the transplant

Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment

Time frame: At any time after HCT

Number of days in the hospital

Time frame: During the first 90 days after HCT

Non-relapse mortality

Time frame: At any time after HCT

Overall survival

Time frame: At any time after HCT

Survival

Time frame: At 200 days after HCT

Safety

Time frame: On or before day 90 after the transplant

Feasibility

Time frame: First 75 days after HCT

Survival without recurrent malignancy

Time frame: At any time after HCT

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes