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 Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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: essential thrombocythemia familial acute myeloid leukemia with mutated CEBPA mycosis fungoides PDGFRA-associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia primary myelofibrosis Sézary syndrome

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Fungal Infections Hodgkin Disease Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes Steroids

Drug Information available for: Methotrexate Beclomethasone dipropionate Methotrexate sodium Beclomethasone dipropionate monohydrate Tacrolimus

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight [ Time Frame: First 75 days after HCT ] [ Designated as safety issue: No ]
Peak and average skin, liver and gut morbidity stages and overall grades [ Time Frame: To day 90 after HCT ] [ Designated as safety issue: No ]
Modified average acute GVHD index score [ Time Frame: To day 90 after HCT ] [ Designated as safety issue: No ]
Cumulative incidence of systemic immunosuppressive treatment for acute GVHD [ Time Frame: At any time after HCT ] [ Designated as 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 [ Time Frame: On or before day 90 after the transplant ] [ Designated as safety issue: No ]
Cumulative incidence of biopsy-proven gastrointestinal GVHD [ Time Frame: On or before day 90 after the transplant ] [ Designated as safety issue: No ]
Proportion of patients with grade IIa GVHD [ Time Frame: On or before day 90 after the transplant ] [ Designated as safety issue: No ]
Proportions of patients with grades IIa and IIb - IV GVHD [ Time Frame: On or before day 90 after the transplant ] [ Designated as safety issue: No ]
Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment [ Time Frame: At any time after HCT ] [ Designated as safety issue: No ]
Number of days in the hospital [ Time Frame: During the first 90 days after HCT ] [ Designated as safety issue: No ]
Non-relapse mortality [ Time Frame: At any time after HCT ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: At any time after HCT ] [ Designated as safety issue: No ]
Survival [ Time Frame: At 200 days after HCT ] [ Designated as safety issue: No ]
Safety [ Time Frame: On or before day 90 after the transplant ] [ Designated as safety issue: Yes ]
Feasibility [ Time Frame: First 75 days after HCT ] [ Designated as safety issue: No ]
Survival without recurrent malignancy [ Time Frame: At any time after HCT ] [ Designated as safety issue: No ]

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

Genders Eligible for Study:	Both
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

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

Martin, Paul

Investigators

Principal Investigator:

Paul Martin

Fred Hutchinson Cancer Research Center

More Information

No publications provided

Responsible Party:	Martin, Paul, Member, Fred Hutchinson Cancer Research Center, 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:	August 21, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Mycosis Fungoides
Congenital Abnormalities
Primary Myelofibrosis
Blast Crisis
Burkitt Lymphoma
Graft vs Host Disease
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Chronic
Leukemia, Neutrophilic, Chronic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Multiple Myeloma
Neoplasms, Plasma Cell
Mycoses
Myelodysplastic Syndromes
Preleukemia

ClinicalTrials.gov processed this record on May 16, 2013