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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Martin, Paul, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00489203
First received: June 20, 2007
Last updated: August 21, 2012
Last verified: August 2012
  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:

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

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
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
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 August 28, 2014