CancerPhase 2NCT00357084

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

A Phase 2 study testing methotrexate, methylprednisolone and prednisone in people with Cancer, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Cancer
What is being tested?: methotrexate, methylprednisolone and prednisone
How many people: 53 participants
Where: 1 siteUnited States
Study dates: May 2006to Aug 2007
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024

Other trials in United States

About this study

Official title: A Phase II Study to Evaluate Efficacy and Tolerability of Methotrexate in Combination With Glucocorticoids for the Treatment of Newly Diagnosed Acute Graft-Versus-Host Disease After Nonmyeloablative Hematopoietic Cell Transplantation

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.

Read the 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
Being tested: methotrexate, methylprednisolone, prednisone
Keywords: graft versus host disease, 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), accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, 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, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, chronic phase chronic myelogenous leukemia, de novo myelodysplastic syndromes
Medical subject headings: Neoplasms, Graft vs Host Disease, Congenital Abnormalities, Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Pdgfra-Associated Chronic Eosinophilic Leukemia, Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of patients treated with a methylprednisolone-equivalent glucocorticoid dose ≤ 0.75 mg/kg on day 28 after initiation of systemic glucocorticoid therapy for acute graft-versus-host disease (GVHD)

Secondary outcomes (9)

Proportion of patients in whom methotrexate (MTX) had to be discontinued because of toxicity
Incidence of severe acute GVHD (grades III or IV)
Incidence of extensive chronic GVHD
Incidence of secondary systemic immunosuppressive therapy
Cumulative corticosteroid use over 1 year
Nonrelapsing mortality at 1 year
Incidence of invasive mold infections
Incidence of recurrent/progressive malignancy
Cumulative dose of methylprednisolone-equivalent treatment during the first 8 weeks after enrollment in patients who survive to day 56

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2006Aug 2007

First posted27 Jul 2006 (estimated)
Study startMay 2006
Primary completionAug 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Enrolment: 53 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00357084
Sponsor's protocol ID: 1978.00
Other IDs: FHCRC-1978.00, CDR0000488486
Status last verified: Sep 2010
First submitted: 26 Jul 2006
Last updated: 14 Sep 2010
Results posted: No