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NCT Number: NCT00410657

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

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.

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Key information

Conditions

Breast Cancer Aberrant Motor Behavior in Dementia Adnexal Diseases Aggression Behavior Behavioral Symptoms Blast Crisis Blood Protein Disorders Bone Marrow Diseases Breast Diseases Breast Neoplasms Burkitt Lymphoma Carcinogenesis Carcinoma Carcinoma, Ovarian Epithelial Cardiovascular Diseases Cell Transformation, Neoplastic Chronic Disease Chronic Myeloproliferative Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Virus Infections Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Epstein-Barr Virus Infections Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gestational Trophoblastic Disease Gestational Trophoblastic Tumor Gonadal Disorders Graft Versus Host Disease Graft vs Host Disease Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Neutrophilic, Chronic Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Multiple Myeloma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Plasma Cell Neoplastic Processes Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Pregnancy Complications Pregnancy Complications, Neoplastic Primary Myelofibrosis Skin Diseases Skin and Connective Tissue Diseases Social Behavior Testicular Diseases Testicular Germ Cell Tumor Testicular Neoplasms Trophoblastic Neoplasms Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Vascular Diseases Virus Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Alemtuzumab

Biological

methylprednisolone

Drug

Prednisone

Drug

flow cytometry

Other

immunologic technique

Other

pharmacological study

Other

Primary outcomes

  1. 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 outcomes

  1. Total cumulative dose of MP-equivalent treatment during the first 8 weeks after study entry

  2. Proportion of patients with complete response, measured weekly through day 56

  3. Incidence of secondary systemic therapy for acute GVHD

  4. Cumulative acute GVHD activity index score at day 56

  5. Incidence of chronic GVHD at 1 year

  6. Nonrelapsing mortality at 1 year

  7. Survival at 1 year

  8. Cumulative incidence of opportunistic infections at 1 year

  9. Cumulative incidence of recurrent or progressive malignancy at 1 year

  10. Peripheral blood CD4, CD8, CD19, and CD16/56 counts at baseline and then periodically for 1 year

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2006
First posted
Dec 13, 2006
Registry last updated
May 14, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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