Campath in Chronic GVHD
Condition: Chronic Graft-vs.-Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Alemtuzumab (Campath)
Intervention description: An escalating dose given over 4 weeks
Intervention MeSH terms: Alemtuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Graft-vs-Host Disease

Summary:

      The CD52 antigen, which is targeted by alemtuzumab, is highly expressed on mature T
      lymphocytes, monocytes and monocyte-derived dendritic cells as well as on mature B cells. Due
      to its more promiscuous effect on immune cells, alemtuzumab not only targets antibody
      producing B lymphocytes as does rituximab, but also targets alloreactive T lymphocytes and
      dendritic cells that also contribute to the complex pathogenesis of chronic GVHD.

      Our hypothesis is that alemtuzumab will be effective in the treatment of chronic GVHD through
      its promiscuous depletion of alloreactive T lymphocytes, dendritic cells as well as antibody
      producing mature B-lymphocytes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recipients of allogeneic stem cell transplantation using myeloablative or
             non-myeloablative conditioning regimens.

          -  Patients must be at least 180 days (6 months) from the allogeneic stem cell
             transplantation procedure.

          -  Patients must have steroid refractory chronic GVHD, defined as having persistent signs
             and symptoms of chronic GVHD despite the use of prednisone at < 0.5 mg/kg/day or 1
             mg/kg every other day for at least 4 weeks in the preceding 12 months (or equivalent
             dosing of alternate corticosteroids) without complete resolution of signs and
             symptoms. Patients with either extensive chronic GVHD or limited chronic GVHD
             requiring systemic therapy are eligible.

          -  Stable dose of corticosteroids for 4 weeks prior to enrollment.

          -  Less than 2mg/kg/day prednisone use (or equivalent).

          -  No addition or subtraction of other immunosuppressive medications (e.g. calcineurin
             inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The
             dose of immunosuppressive medicines may be adjusted based on the therapeutic range of
             that drug.

          -  Adequate bone marrow function indicated by:

          -  ANC>1000/mm3

          -  Platelets>50,000/mm3

          -  Men and women of reproductive potential must agree to use an acceptable method of
             birth control during treatment and for six months after completion of treatment

        Exclusion Criteria:

          -  Prednisone requirement>2mg/kg/day or equivalent

          -  Known life-threatening hypersensitivity to alemtuzumab, other anti-B cell or anti-T
             cell antibodies.

          -  Prior exposure to any new immunosuppressive medication (or Extra Corporeal
             Phototherapy) in the preceding 4 weeks prior to enrollment.

          -  Active, uncontrolled infection.

          -  History of Hepatitis B or C infection.

          -  Active malignant disease relapse.

          -  Donor lymphocyte infusion within the preceding 100 days or plan for donor lymphocyte
             infusion in the coming 3 months.

          -  Life expectancy <3 months.

          -  Pregnancy or lactation.

          -  Evidence of HIV seropositivity.

          -  Inability to comply with alemtuzumab treatment regimen.