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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00357084
First received: July 26, 2006
Last updated: September 10, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: methotrexate
Drug: methylprednisolone
Drug: prednisone
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Supportive Care
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

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U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients in whom methotrexate (MTX) had to be discontinued because of toxicity [ Designated as safety issue: Yes ]
  • Incidence of severe acute GVHD (grades III or IV) [ Designated as safety issue: Yes ]
  • Incidence of extensive chronic GVHD [ Designated as safety issue: Yes ]
  • Incidence of secondary systemic immunosuppressive therapy [ Designated as safety issue: Yes ]
  • Cumulative corticosteroid use over 1 year [ Designated as safety issue: No ]
  • Nonrelapsing mortality at 1 year [ Designated as safety issue: Yes ]
  • Incidence of invasive mold infections [ Designated as safety issue: Yes ]
  • Incidence of recurrent/progressive malignancy [ Designated as safety issue: Yes ]
  • Cumulative dose of methylprednisolone-equivalent treatment during the first 8 weeks after enrollment in patients who survive to day 56 [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: May 2006
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357084

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Marco B. Mielcarek, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Marco B. Mielcarek, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00357084     History of Changes
Other Study ID Numbers: 1978.00, FHCRC-1978.00, CDR0000488486
Study First Received: July 26, 2006
Last Updated: September 10, 2010
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
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
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
juvenile myelomonocytic 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 mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:
Graft vs Host Disease
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Immune System Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Glucocorticoids
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Prednisone
Methotrexate
Methylprednisolone acetate
Prednisolone acetate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 21, 2014