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A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease


Phase 2
N/A
N/A
Not Enrolling
Both
Breast Cancer, Chronic Myeloproliferative Disorders, Gestational Trophoblastic Tumor, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases, Neuroblastoma, Ovarian Cancer, Testicular Germ Cell Tumor

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Trial Information

A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease


OBJECTIVES:

- Determine whether the administration of low-dose alemtuzumab at the onset of acute
graft-versus-host disease can accelerate withdrawal of glucocorticoids and decrease
nonrelapsing mortality in patients who have undergone myeloablative allogeneic stem
cell transplantation.

OUTLINE: This is an open-label, nonrandomized study.

Within 72 hours of beginning glucocorticoid therapy, patients receive alemtuzumab IV over at
least 2 hours on days 1 and 2. If graft-versus-host disease (GVHD) responds well during days
1-14 but returns between days 28 and 56, patients are eligible to receive 2 additional doses
of alemtuzumab.

Patients receive glucocorticoid therapy comprising methylprednisolone IV or oral prednisone
daily until objective evidence of improvement in manifestations of GVHD. Patients with
resolved or significantly improved GVHD receive treatment until day 10 followed by an
accelerated taper until day 72 if no flare up of GVHD occurs during the glucocorticoid
taper. Patients with recurrent or progressive GVHD during the accelerated taper are treated
for 5-7 days before resuming a less rapid taper. Patients with no improvement may receive
secondary therapy with alternative immunosuppressive medications at the discretion of the
managing physician. Treatment continues in the absence of progressive GVHD of at least 3
days duration during days 2-10; persisting GVHD without improvement between days 10-14;
recurrent or progressive GVHD after day 10 that does not respond within 3 days to topical
immunosuppressive therapy; and/or an increase in the systemic glucocorticoid dose by two
taper steps; or unacceptable toxicity.

Patients undergo blood collection at baseline and then periodically during study treatment
for pharmacokinetics and quantification of viral loads for human herpes virus 6, adenovirus,
Epstein-Barr virus, and cytomegalovirus. Samples are also examined by flow cytometry for B-
and T-cell quantification at baseline, periodically during study treatment, and at 1 year
after transplantation.

After completion of study treatment, patients are followed periodically.

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)

- Grade IIB-IV disease

- Requires glucocorticoids for treatment of GVHD, as indicated by 1 of the following:

- Initial treatment with prednisone or methylprednisolone at 2 mg/kg is indicated
(in the judgement of the 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 hematopoietic stem cell transplantation
(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 the attending physician)

- Has undergone allogeneic HSCT with myeloablative conditioning

- No nonmyeloablative conditioning or autologous HSCT

- No primary treatment of acute GVHD with methylprednisolone at any of the following
doses:

- More than 2 mg/kg/day at any time

- 2 mg/kg/day for > 72 hours

- 1 mg/kg/day for > 96 hours

- No presence of distinctive or diagnostic manifestations of chronic GVHD

- No relapsed, refractory, or secondary malignancy

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) 20-100% OR Lanksy PS 20-100%

- Life expectancy ≥ 1 month

- Absolute neutrophil count ≥ 500/mm^3

- Negative pregnancy test

- No Mini Mental State Exam score < 24/30 or confusion (for patients > 12 years of age)

- No history of type I hypersensitivity reaction to alemtuzumab or any of its
components

- No increasing levels of viremia by serial quantitative viral plasma polymerase chain
reaction assays

- No invasive viral or fungal disease that does not respond to appropriate antiviral or
antifungal medications

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No systemic immunosuppression tapered or stopped for treatment of leukemic relapse or
minimal residual disease

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Proportion of patients with methylprednisolone (MP)-equivalent glucocorticoid doses ≤ 0.75 mg/kg on day 28 after starting therapy for graft-versus-host disease (GVHD)

Principal Investigator

Paul Carpenter, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

2096.00

NCT ID:

NCT00410657

Start Date:

July 2006

Completion Date:

Related Keywords:

  • Breast Cancer
  • Chronic Myeloproliferative Disorders
  • Gestational Trophoblastic Tumor
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • Neuroblastoma
  • Ovarian Cancer
  • Testicular Germ Cell Tumor
  • 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 chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • chronic eosinophilic leukemia
  • chronic idiopathic myelofibrosis
  • chronic myelomonocytic leukemia
  • chronic neutrophilic 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
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • splenic marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • poor prognosis metastatic gestational trophoblastic tumor
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage II ovarian epithelial cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • aggressive, noncontiguous stage II adult non-Hodgkin lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • stage III malignant testicular germ cell tumor
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • childhood acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood myelodysplastic syndromes
  • Breast Neoplasms
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Neuroblastoma
  • Ovarian Neoplasms
  • Trophoblastic Neoplasms
  • Lymphoma, Large-Cell, Immunoblastic
  • Neoplasms, Germ Cell and Embryonal
  • Gestational Trophoblastic Neoplasms
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109