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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


Phase 2
N/A
N/A
Not Enrolling
Both
Cancer

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Supportive Care

Outcome Measure:

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)

Safety Issue:

No

Principal Investigator

Marco B. Mielcarek, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1978.00

NCT ID:

NCT00357084

Start Date:

May 2006

Completion Date:

Related Keywords:

  • Cancer
  • 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
  • noncontiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • poor prognosis metastatic gestational trophoblastic tumor
  • previously treated childhood rhabdomyosarcoma
  • previously treated myelodysplastic syndromes
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult Burkitt lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood rhabdomyosarcoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent small lymphocytic lymphoma
  • recurrent Wilms tumor and other childhood kidney tumors
  • refractory chronic lymphocytic leukemia
  • refractory hairy cell leukemia
  • refractory multiple myeloma
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • secondary myelodysplastic syndromes
  • splenic marginal zone lymphoma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage II ovarian epithelial cancer
  • stage III adult Burkitt lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III multiple myeloma
  • stage III small lymphocytic lymphoma
  • stage III malignant testicular germ cell tumor
  • stage IV adult Burkitt lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV chronic lymphocytic leukemia
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • Waldenstrom macroglobulinemia
  • childhood myelodysplastic syndromes
  • Graft vs Host Disease
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109