Skip to main content
OpenTrials
Completed

NCT Number: NCT00357084

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Cancer Adnexal Diseases Blast Crisis Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Carcinogenesis Carcinoma Carcinoma, Ovarian Epithelial Cardiovascular Diseases Cell Transformation, Neoplastic Chronic Disease Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Epstein-Barr Virus Infections Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gonadal Disorders Graft vs Host Disease Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Infections Kidney Diseases Kidney Neoplasms Leukemia Leukemia, B-Cell Leukemia, Hairy Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Neutrophilic, Chronic Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoproliferative Disorders Male Urogenital Diseases Multiple Myeloma Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Complex and Mixed Neoplasms, Glandular and Epithelial Neoplasms, Plasma Cell Neoplastic Processes Neoplastic Syndromes, Hereditary Ovarian Diseases Ovarian Neoplasms Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Primary Myelofibrosis Recurrence Sezary Syndrome Testicular Diseases Testicular Neoplasms Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia Wilms Tumor

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

methotrexate

Drug

methylprednisolone

Drug

Prednisone

Drug

Primary outcomes

  1. 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

  1. Proportion of patients in whom methotrexate (MTX) had to be discontinued because of toxicity

  2. Incidence of severe acute GVHD (grades III or IV)

  3. Incidence of extensive chronic GVHD

  4. Incidence of secondary systemic immunosuppressive therapy

  5. Cumulative corticosteroid use over 1 year

  6. Nonrelapsing mortality at 1 year

  7. Incidence of invasive mold infections

  8. Incidence of recurrent/progressive malignancy

  9. Cumulative dose of methylprednisolone-equivalent treatment during the first 8 weeks after enrollment in patients who survive to day 56

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2007
First posted
Jul 27, 2006
Registry last updated
Sep 14, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.