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Trial record 25 of 53 for:    "Adult Acute Lymphocytic Leukemia" | "Methylprednisolone hemisuccinate"

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

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ClinicalTrials.gov Identifier: NCT00357084
Recruitment Status : Completed
First Posted : July 27, 2006
Last Update Posted : September 14, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE July 26, 2006
First Posted Date  ICMJE July 27, 2006
Last Update Posted Date September 14, 2010
Study Start Date  ICMJE May 2006
Actual Primary Completion Date August 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
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)
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00357084 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
  • 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methotrexate and Glucocorticoids in Treating Patients With Newly Diagnosed Acute Graft-Versus-Host Disease After Donor Stem Cell Transplant
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Supportive Care
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: methotrexate
  • Drug: methylprednisolone
  • Drug: prednisone
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
53
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date August 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00357084
Other Study ID Numbers  ICMJE 1978.00
FHCRC-1978.00
CDR0000488486 ( Registry Identifier: PDQ )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marco B. Mielcarek, Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Marco B. Mielcarek, MD Fred Hutchinson Cancer Research Center
PRS Account Fred Hutchinson Cancer Research Center
Verification Date September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP