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

Purpose

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.

Condition	Intervention	Phase
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	Drug: beclomethasone dipropionate Drug: placebo Drug: tacrolimus Drug: methotrexate Procedure: allogeneic hematopoietic stem cell transplantation	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
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

Resource links provided by NLM:

Genetics Home Reference related topics: Sézary syndrome multiple myeloma mycosis fungoides

Drug Information available for: Beclomethasone dipropionate Beclomethasone dipropionate monohydrate

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Hodgkin Lymphoma Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic B-cell Lymphoma Mantle Cell Lymphoma Chronic Myeloid Leukemia Diffuse Large B-Cell Lymphoma Myelodysplastic/myeloproliferative Disease Multiple Myeloma Leukemia, T-cell, Chronic Follicular Lymphoma Childhood Acute Lymphoblastic Leukemia Cutaneous T-cell Lymphoma Essential Thrombocythemia Homologous Wasting Disease Adult T-cell Leukemia/lymphoma Burkitt Lymphoma Myelofibrosis Marginal Zone Lymphoma Acute Graft Versus Host Disease Hodgkin Lymphoma, Childhood Lymphoma, Large-cell Anaplastic Plasmacytoma Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Lymphoblastic Lymphoma Mycosis Fungoides Sezary Syndrome Lymphomatoid Granulomatosis Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Hairy Cell Leukemia Chronic Neutrophilic Leukemia Chronic Myeloproliferative Disorders Hypereosinophilic Syndrome

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

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 Measures:

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 ]


Enrollment:	140
Study Start Date:	April 2007
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: BECLOMETH Beclovent Beconase Qvar Vancenase Vanceril Drug: tacrolimus Given after transplant Other Names: Advagraf FK 506 Prograf Protopic Drug: methotrexate Given after transplant Other Names: Abitrexate amethopterin Folex methylaminopterin Mexate MTX 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 Name: PLCB Drug: tacrolimus Given after transplant Other Names: Advagraf FK 506 Prograf Protopic Drug: methotrexate Given after transplant Other Names: Abitrexate amethopterin Folex methylaminopterin Mexate MTX Procedure: allogeneic hematopoietic stem cell transplantation Undergo stem cell transplant

Arms

Assigned Interventions

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:

BECLOMETH
Beclovent
Beconase
Qvar
Vancenase
Vanceril

Drug: tacrolimus

Given after transplant

Other Names:

Advagraf
FK 506
Prograf
Protopic

Drug: methotrexate

Given after transplant

Other Names:

Abitrexate
amethopterin
Folex
methylaminopterin
Mexate
MTX

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 Name: PLCB

Drug: tacrolimus

Given after transplant

Other Names:

Advagraf
FK 506
Prograf
Protopic

Drug: methotrexate

Given after transplant

Other Names:

Abitrexate
amethopterin
Folex
methylaminopterin
Mexate
MTX

Procedure: allogeneic hematopoietic stem cell transplantation

Undergo stem cell transplant

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.

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489203

Locations


United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

Investigators


Principal Investigator:	Paul Martin	Fred Hutchinson Cancer Research Center

More Information


Responsible Party:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00489203 History of Changes
Other Study ID Numbers:	2079.00 NCI-2009-01544
Study First Received:	June 20, 2007
Last Updated:	March 5, 2015

Additional relevant MeSH terms:


Mycosis Fungoides Lymphoma Syndrome Leukemia Leukemia, Myeloid Multiple Myeloma Neoplasms, Plasma Cell Leukemia, Myeloid, Acute Lymphoma, Follicular Lymphoma, Non-Hodgkin Myelodysplastic Syndromes Preleukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell	Hodgkin Disease Lymphoma, B-Cell Lymphoma, Mantle-Cell Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma, B-Cell, Marginal Zone Lymphoma, Large B-Cell, Diffuse Burkitt Lymphoma Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Graft vs Host Disease Mycoses Primary Myelofibrosis Lymphoma, T-Cell Sezary Syndrome Leukemia, Myelomonocytic, Acute

ClinicalTrials.gov processed this record on August 18, 2017