• Engraftment measured by donor-host chimerism in lymphoid and myeloid lines at days 15, 30, 45, 60, and 100 [ Designated as safety issue: No ]
• Response (complete [CR] and partial responses [PR] and stable [SD] or progressive disease [PD]) at days 30, 60, and 100 [ Designated as safety issue: No ]

• Engraftment measured by donor-host chimerism in lymphoid and myeloid lines at days 15, 30, 45, 60, and 100
• Response (complete [CR] and partial responses [PR] and stable [SD] or progressive disease [PD]) at days 30, 60, and 100

• Immune reconstitution measured by lymphocyte subset analysis and T cell repertoire at days 15, 30, 45, 60, and 100 [ Designated as safety issue: No ]
• Safety measured by incidence and severity of post-transplant complications [ Designated as safety issue: Yes ]

• Immune reconstitution measured by lymphocyte subset analysis and T cell repertoire at days 15, 30, 45, 60, and 100
• Safety measured by incidence and severity of post-transplant complications

RATIONALE: Monoclonal antibodies such as alemtuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Allogeneic peripheral stem cell transplantation may be able to replace immune cells that were destroyed by the anticancer therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and cyclosporine may prevent this rejection.

PURPOSE: This phase I/II trial is studying how well giving alemtuzumab together with chemotherapy and donor peripheral stem cell transplantation works in treating patients with advanced mycosis fungoides and/or Sezary syndrome.

OBJECTIVES:

• Evaluate the ability of a conditioning regimen comprising alemtuzumab and fludarabine with or without cyclophosphamide to produce at least 80% sustained engraftment in patients with advanced mycosis fungoides/Sezary syndrome.
• Evaluate allogeneic graft-versus-tumor effects in mycosis fungoides/Sezary syndrome patients treated with a nonmyeloablative conditioning regimen followed by HLA-matched allogeneic peripheral blood stem cell transplantation.
• Determine the safety and toxicity of this regimen in these patients.
• Determine tumor response, disease-free survival, and overall survival of patients treated with this regimen.
• Determine the rate and extent of lymphocyte subset reconstitution in patients treated with this regimen.
• Determine transplant-related morbidity, including rates of acute and chronic graft-versus-host disease and infectious complications, and mortality in patients treated with this regimen.

OUTLINE: Patients receive 1 of 2 nonmyeloablative conditioning regimens, depending on engraftment efficacy in prior patients.

• Regimen A: Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15 and fludarabine IV over 30 minutes on days -5 to -1.
• Regimen B: Patients receive alemtuzumab and fludarabine as in regimen A plus cyclophosphamide IV over 1 hour on days -7 and -6.

Patients also receive graft-versus-host disease prophylaxis comprising oral cyclosporine twice a day beginning on day -4 and continuing until day 100.

Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

Donor T cell and myeloid chimerism will be evaluated and will guide decisions regarding donor lymphocyte infusions.

Patients are followed every 2 months for 6 months, every 3 months for 1.5 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 9-58 patients will be accrued for this study.

• Biological: alemtuzumab
• Drug: cyclophosphamide
• Drug: fludarabine phosphate

• Experimental: Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15 and fludarabine IV over 30 minutes on days -5 to -1.
• Experimental: Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15; fludarabine IV over 30 minutes on days -5 to -1; and cyclophosphamide IV over 1 hour on days -7 and -6.

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Histologically confirmed mycosis fungoides (MF)

    • Stage IIB, III, IVA, or IVB
    • Progressive disease after at least 1 treatment regimen
  • Sezary syndrome (SS)
• Clinically or radiographically evaluable disease
• Anticipated median survival of less than 5 years or debilitation as result of disease
• Less than 25% of liver involved with metastatic tumor by CT scan
• No CNS metastases by MRI
• 6/6 HLA-matched family donor available

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Performance status

• ECOG 0-1

Life expectancy

• See Disease Characteristics
• At least 3 months

Hematopoietic

• Not specified

Hepatic

• See Disease Characteristics
• Bilirubin no greater than 4 mg/dL
• Transaminases no greater than 5 times upper limit of normal

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• LVEF at least 40%

Pulmonary

• DLCO at least 60% of predicted

Other

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• No major organ dysfunction or failure or major anticipated illness that would preclude transplantation
• No psychiatric disorder or mental deficiency that would preclude study
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 30 days since prior therapy for MF or SS