Official Title: “A Phase II Study to Evaluate the Efficacy of Oral Beclomethasone Dipropionate for Prevention of Acute GVHD After Hematopoietic Cell Transplantation With Myeloablative Conditioning Regimens”

RATIONALE: Beclomethasone may be effective in preventing acute graft-versus-host disease in patients undergoing a donor stem cell transplant for hematologic cancer.

PURPOSE: This randomized phase II trial is studying how well beclomethasone works in preventing acute graft-versus-host disease in patients undergoing a donor stem cell transplant for hematologic cancer.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Active Control

Study Primary Completion Date: December 2009

OBJECTIVES: - Assess the efficacy of beclomethasone dipropionate in preventing acute graft-vs-host disease in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation for hematologic cancer.

OUTLINE: This is a randomized, double-blind, controlled study. Patients are stratified according to type of donor (related vs unrelated) and disease type and stage (chronic myeloid leukemia in chronic phase, refractory anemia without excess blasts, or other hematologic malignancy in remission vs more advanced malignancy). 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 an oral placebo 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplantation. 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.

Intervention(s) in this Clinical Trial

• Drug: beclomethasone dipropionate
  • Given orally before and after transplant
• Drug: methotrexate
  • Given after transplant
• Drug: placebo
  • Given orally before and after transplant
• Drug: tacrolimus
  • Given after transplant

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• Active Comparator: Arm II
  • Patients receive an oral placebo 4 times daily beginning at the start of the conditioning regimen and continuing through day 75 post-transplantation. Patients also receive a standard immunosuppressive regimen comprising tacrolimus and methotrexate post-transplant.

Primary Measures

• Development of acute graft-vs-host disease (GVHD) with severity sufficient to require systemic immunosuppressive treatment on or before day 90 post-transplant
  • Safety Issue?: No

Secondary Measures

• Safety
  • Safety Issue?: Yes
• Feasibility
  • Safety Issue?: No
• Cumulative glucocorticoid dose per kg body weight during the first 75 days post-transplant
  • Safety Issue?: No
• Peak and average skin, liver, and gut morbidity stages and overall grades during the first 90 days post-transplant
  • Safety Issue?: No
• Modified average acute GVHD index score during the first 90 days post-transplant
  • Safety Issue?: No
• Cumulative incidence of systemic immunosuppressive treatment for acute GVHD at any time post-transplant
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• Cumulative incidence of biopsy-proven gastrointestinal GVHD
  • Safety Issue?: No
• Proportion of patients with grade IIa and/or IIb-IV GVHD
• Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment
  • Safety Issue?: No
• Number of days in the hospital during the first 90 days post-transplant
  • Safety Issue?: No
• Non-relapse mortality
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Survival at 200 days post-transplant
  • Safety Issue?: No
• Survival without recurrent malignancy
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of a hematologic malignancy
• Meets all of the following criteria:
• Undergoing or planning to undergo allogeneic hematopoietic stem cell transplantation with marrow or growth factor-mobilized peripheral blood stem cells from HLA-A, -B, -C, -DRB1, and HLA-DQB1-allele matched or single-allele or antigen mismatched related or unrelated donor
• Received or planning to receive myeloablative pretransplant conditioning regimen with > 800 Gy total-body irradiation and cyclophosphamide OR high-dose busulfan and cyclophosphamide
• Received or planning to receive methotrexate and tacrolimus for prevention of graft-vs-host disease (GVHD) post-transplant

PATIENT CHARACTERISTICS:

• Body weight ≥ 35 kg
• Able to tolerate oral administration of study drug during first 2 weeks post-transplant
• No concurrent incarceration
• No hospitalization at beginning of pretransplant conditioning regimen due to preexisting medical complications
• No known intolerance to beclomethasone dipropionate
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 3 months since prior rabbit antithymocyte globulin (ATG) or alemtuzumab
• No prior T-cell depletion or rabbit ATG to prevent acute GVHD
• No prior participation in another clinical trial with a primary endpoint related to acute GVHD
• No concurrent glucocorticoids at prednisone-equivalent doses > 0.2 mg/kg/day
• No concurrent cord blood transplantation

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Fred Hutchinson Cancer Research Center

Overall Clinical Trial Officials and Contacts

Paul J. Martin, MD Principal Investigator Fred Hutchinson Cancer Research Center  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00489203

Study ID Number: CDR0000549680

ClinicalTrials.gov Identifier: NCT00489203

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database