Alemtuzumab and Glucocorticoids in Treating Newly Diagnosed Acute Graft-Versus-Host Disease in Patients Who Have Undergone a Donor Stem Cell Transplant

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00410657
First received: December 11, 2006
Last updated: May 12, 2010
Last verified: May 2010
  Purpose

RATIONALE: Alemtuzumab and glucocorticoids, 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 alemtuzumab together with glucocorticoids works in treating newly diagnosed acute graft-versus-host disease in patients who have undergone donor stem cell transplant.


Condition Intervention Phase
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
Biological: alemtuzumab
Drug: methylprednisolone
Drug: prednisone
Other: flow cytometry
Other: immunologic technique
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Multiple Myeloma Myelodysplastic Syndromes Chronic Myeloproliferative Disorders Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse B-cell Lymphomas Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Ovarian Cancer Leukemia, Myeloid Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Myelodysplastic/myeloproliferative Disease Homologous Wasting Disease Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Myeloid Leukemia, Adult Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Hodgkin Lymphoma Neuroblastoma Gestational Trophoblastic Tumor Follicular Lymphoma Ovarian Epithelial Cancer Mantle Cell Lymphoma Acute Graft Versus Host Disease Myelofibrosis Burkitt Lymphoma Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Lymphoma, Large-cell Testicular Cancer Lymphoblastic Lymphoma Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Hypereosinophilic Syndrome Chronic Neutrophilic Leukemia Anaplastic Plasmacytoma Hydatidiform Mole Neuroepithelioma
U.S. FDA Resources

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

Primary Outcome Measures:
  • 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)

Secondary Outcome Measures:
  • Total cumulative dose of MP-equivalent treatment during the first 8 weeks after study entry
  • Proportion of patients with complete response, measured weekly through day 56
  • Incidence of secondary systemic therapy for acute GVHD
  • Cumulative acute GVHD activity index score at day 56
  • Incidence of chronic GVHD at 1 year
  • Nonrelapsing mortality at 1 year
  • Survival at 1 year
  • Cumulative incidence of opportunistic infections at 1 year
  • Cumulative incidence of recurrent or progressive malignancy at 1 year
  • Peripheral blood CD4, CD8, CD19, and CD16/56 counts at baseline and then periodically for 1 year

Estimated Enrollment: 53
Study Start Date: July 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00410657

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Paul Carpenter, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00410657     History of Changes
Other Study ID Numbers: 2096.00, FHCRC-2096.00, CDR0000523371
Study First Received: December 11, 2006
Last Updated: May 12, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

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 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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Ovarian Neoplasms
Myelodysplastic Syndromes
Preleukemia
Neuroblastoma
Graft vs Host Disease
Lymphoma
Leukemia
Syndrome
Breast Neoplasms
Neoplasms
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Myeloproliferative Disorders
Plasmacytoma
Trophoblastic Neoplasms
Gestational Trophoblastic Disease
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 02, 2014