Methotrexate and Glucocorticoids in Treating Patients With Newly Diagnosed Acute Graft-Versus-Host Disease After Donor Stem Cell Transplant

NCT ID: NCT00357084

Last Updated: 2010-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31

Brief Summary

RATIONALE: Methotrexate and glucocorticoid therapy, such as prednisone or methylprednisolone, may be an effective treatment for acute graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This phase II trial is studying how well giving methotrexate together with glucocorticoids works in treating patients with newly diagnosed acute graft-versus-host disease after donor stem cell transplant.

Detailed Description

OBJECTIVES:

• Determine, within the limits of a phase II study, whether low-dose methotrexate can accelerate withdrawal of glucocorticoids and decrease nonrelapsing mortality in patients with newly diagnosed acute graft-versus-host disease (GVHD) who have undergone nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT).
• Determine the tolerability of low-dose methotrexate and glucocorticoids in treating newly diagnosed acute GVHD in these patients.

OUTLINE: This is a cohort study. Patients receive concurrent low-dose methotrexate and a glucocorticoid for treatment of acute graft-versus-host disease (GVHD).

Patients receive the first dose of methotrexate IV ≥ 12 hours before initiation of glucocorticoid treatment (if glucocorticoid treatment has not been initiated) and the second dose 72 hours after dose 1. Patients then receive subsequent doses of methotrexate IV or orally once weekly for up to 1 year* until resolution of GVHD in the absence of recurrent malignancy, refractory or chronic GVHD, administration of secondary treatment for GVHD, or unacceptable toxicity.

NOTE: *Treatment with low-dose MTX may continue beyond 1 year at the discretion of the managing physician.

Patients receive glucocorticoid therapy comprising prednisone or methylprednisolone IV twice daily until objective evidence of improvement in GVHD manifestation. Patients with resolved or significantly improved GVHD receive treatment for 10 days followed by an accelerated taper for a total of 72 days of treatment in case of no flare up of GVHD during the glucocorticoid taper. Patients with exacerbation or recurrence of GVHD during the accelerated taper are treated for ≥ 1 week before resuming a less rapid taper. Patients who develop GVHD progression or primary refractory GVHD may receive secondary systemic therapy at the discretion of the managing physician.

After completion of study treatment, patients are followed at 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Conditions

Cancer

Study Design

• Primary Study Purpose: SUPPORTIVE_CARE

Interventions

methotrexate

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed acute graft-versus-host disease (GVHD)
• Has undergone nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched related or unrelated donor ≥ 14 days ago
• Treatment of GVHD with glucocorticoids indicated by 1 of the following criteria:

• Initial treatment with prednisone or methylprednisolone at 2 mg/kg indicated (in the judgement of attending physician) by any of the following:

• Severity of GVHD requires hospitalization
• GVHD manifestations include symptoms other than anorexia, nausea, and vomiting
• GVHD begins within 2-3 weeks after HSCT
• GVHD manifestations progress rapidly from 1 day to the next before treatment
• Initial treatment with prednisone or methylprednisolone at 1 mg/kg did not produce adequate clinical improvement within the first 4 days (in the judgement of attending physician)
• No pleural effusion or ascites (i.e., free-flowing fluid by lateral decubitus views)

• Mere blunting of costo-phrenic angles on a posterior anterior chest x-ray is not sufficient
• No GVHD after donor lymphocyte infusion
• No hallmarks of chronic GVHD
• No bronchiolitis obliterans

PATIENT CHARACTERISTICS:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No severe mucositis (grade 3 or 4) indicated by erythema, edema, or ulcerations requiring hydration, parenteral nutritional support, or intubation or resulting in aspiration pneumonia
• Absolute neutrophil count ≥ 1,500/mm^3
• Bilirubin ≤ 2 times upper limit of normal (ULN) (unless abnormality attributable to GVHD)
• AST and ALT ≤ 2 times ULN (unless abnormality attributable to GVHD)
• Creatinine clearance ≥ 50 mL/min

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior prednisone or methylprednisolone at 2 mg/kg for > 72 hours or at 1 mg/kg for > 96 hours
• Concurrent topical therapy, including psoralen and ultraviolet A irradiation (PUVA), glucocorticoid creams, oral beclomethasone dipropionate, topical azathioprine, or ophthalmic glucocorticoids allowed
• No other concurrent treatment for GVHD

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Fred Hutchinson Cancer Research Center

Principal Investigators

Marco B. Mielcarek, MD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Locations

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

FHCRC-1978.00

Identifier Type: -

Identifier Source: secondary_id

CDR0000488486

Identifier Type: REGISTRY

Identifier Source: secondary_id

1978.00

Identifier Type: -

Identifier Source: org_study_id