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

Primary Purpose

Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
beclomethasone dipropionate
placebo
tacrolimus
methotrexate
allogeneic hematopoietic stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hematopoietic/Lymphoid Cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hackensack University Medical Center
  • Fred Hutchinson Cancer Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight
Peak and average skin, liver and gut morbidity stages and overall grades
Modified average acute GVHD index score
Cumulative incidence of systemic immunosuppressive treatment for acute GVHD
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
Cumulative incidence of biopsy-proven gastrointestinal GVHD
Proportion of patients with grade IIa GVHD
Proportions of patients with grades IIa and IIb - IV GVHD
Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment
Number of days in the hospital
Non-relapse mortality
Overall survival
Survival
Safety
Feasibility
Survival without recurrent malignancy

Full Information

First Posted
June 20, 2007
Last Updated
February 1, 2021
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00489203
Brief Title
Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

Data Monitoring Committee
No

5. 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Atypical Chronic Myeloid Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Eosinophilic Leukemia, Chronic Myelomonocytic Leukemia, Chronic Neutrophilic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, Contiguous Stage II Adult Burkitt Lymphoma, Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Contiguous Stage II Adult Lymphoblastic Lymphoma, Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Mantle Cell Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Contiguous Stage II Small Lymphocytic Lymphoma, de Novo Myelodysplastic Syndromes, Essential Thrombocythemia, Extramedullary Plasmacytoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Graft Versus Host Disease, Isolated Plasmacytoma of Bone, Juvenile Myelomonocytic Leukemia, Meningeal Chronic Myelogenous Leukemia, Myelodysplastic/Myeloproliferative Disease, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Stage I Adult Burkitt Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Mixed Cell Lymphoma, Stage I Adult Diffuse Small Cleaved Cell Lymphoma, Stage I Adult Hodgkin Lymphoma, Stage I Adult Immunoblastic Large Cell Lymphoma, Stage I Adult Lymphoblastic Lymphoma, Stage I Adult T-cell Leukemia/Lymphoma, Stage I Childhood Hodgkin Lymphoma, Stage I Chronic Lymphocytic Leukemia, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle Cell Lymphoma, Stage I Marginal Zone Lymphoma, Stage I Multiple Myeloma, Stage I Mycosis Fungoides/Sezary Syndrome, Stage I Small Lymphocytic Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage II Adult T-cell Leukemia/Lymphoma, Stage II Chronic Lymphocytic Leukemia, Stage II Cutaneous T-cell Non-Hodgkin Lymphoma, Stage II Multiple Myeloma, Stage II Mycosis Fungoides/Sezary Syndrome, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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 Title
Arm II
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
beclomethasone dipropionate
Other Intervention Name(s)
BECLOMETH, Beclovent, Beconase, Qvar, Vancenase, Vanceril
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Other Intervention Name(s)
Advagraf, FK 506, Prograf, Protopic
Intervention Description
Given after transplant
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
Abitrexate, amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given after transplant
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo stem cell transplant
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight
Time Frame
First 75 days after HCT
Title
Peak and average skin, liver and gut morbidity stages and overall grades
Time Frame
To day 90 after HCT
Title
Modified average acute GVHD index score
Time Frame
To day 90 after HCT
Title
Cumulative incidence of systemic immunosuppressive treatment for acute GVHD
Time Frame
At any time after HCT
Title
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
Title
Cumulative incidence of biopsy-proven gastrointestinal GVHD
Time Frame
On or before day 90 after the transplant
Title
Proportion of patients with grade IIa GVHD
Time Frame
On or before day 90 after the transplant
Title
Proportions of patients with grades IIa and IIb - IV GVHD
Time Frame
On or before day 90 after the transplant
Title
Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment
Time Frame
At any time after HCT
Title
Number of days in the hospital
Time Frame
During the first 90 days after HCT
Title
Non-relapse mortality
Time Frame
At any time after HCT
Title
Overall survival
Time Frame
At any time after HCT
Title
Survival
Time Frame
At 200 days after HCT
Title
Safety
Time Frame
On or before day 90 after the transplant
Title
Feasibility
Time Frame
First 75 days after HCT
Title
Survival without recurrent malignancy
Time Frame
At any time after HCT

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Martin
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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