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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2

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

Treatments: Drug: placebo; Drug: beclomethasone dipropionate; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: methotrexate; Drug: tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT00489203

2079.00

NCI-2009-01544

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

140 participants in 2 patient groups

Arm I

Experimental group

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.

Treatment:

Drug: tacrolimus

Procedure: allogeneic hematopoietic stem cell transplantation

Drug: methotrexate

Drug: beclomethasone dipropionate

Arm II

Active Comparator group

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.

Treatment:

Drug: tacrolimus

Procedure: allogeneic hematopoietic stem cell transplantation

Drug: methotrexate

Drug: placebo