Clinical trial NCT00489203: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
First posted: 2007-06-21
Enrollment: 140
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Development of acute graft-versus-host disease (GVHD) with severity sufficient to require systemic immunosuppressive treatment
timeFrame: On or before day 90 after the transplant
Secondary outcomes:
measure: Cumulative glucocorticoid dose (measured as prednisone equivalents) per kg body weight
timeFrame: First 75 days after HCT
measure: Peak and average skin, liver and gut morbidity stages and overall grades
timeFrame: To day 90 after HCT
measure: Modified average acute GVHD index score
timeFrame: To day 90 after HCT
measure: Cumulative incidence of systemic immunosuppressive treatment for acute GVHD
timeFrame: At any time after HCT
measure: 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
timeFrame: On or before day 90 after the transplant
measure: Cumulative incidence of biopsy-proven gastrointestinal GVHD
timeFrame: On or before day 90 after the transplant
measure: Proportion of patients with grade IIa GVHD
timeFrame: On or before day 90 after the transplant
measure: Proportions of patients with grades IIa and IIb - IV GVHD
timeFrame: On or before day 90 after the transplant
measure: Cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment
timeFrame: At any time after HCT
measure: Number of days in the hospital
timeFrame: During the first 90 days after HCT
measure: Non-relapse mortality
timeFrame: At any time after HCT
measure: Overall survival
timeFrame: At any time after HCT
measure: Survival
timeFrame: At 200 days after HCT
measure: Safety
timeFrame: On or before day 90 after the transplant
measure: Feasibility
timeFrame: First 75 days after HCT
measure: Survival without recurrent malignancy
timeFrame: At any time after HCT
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Paul Martin
role: PRINCIPAL_INVESTIGATOR
References: